7ukf - Revision history

OCA at 09:38, 14 February 2024

2024-02-14T09:38:34Z

←Older revision		Revision as of 09:38, 14 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7ukf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UKF FirstGlance]. <br>		<table><tr><td colspan='2'>[[7ukf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UKF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.02Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ukf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ukf OCA], [https://pdbe.org/7ukf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ukf RCSB], [https://www.ebi.ac.uk/pdbsum/7ukf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ukf ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ukf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ukf OCA], [https://pdbe.org/7ukf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ukf RCSB], [https://www.ebi.ac.uk/pdbsum/7ukf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ukf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/KCND2_HUMAN KCND2_HUMAN]] KNCD2 mutations have been found in a family with autism and epilepsy and may play a role in disease pathogenesis. Autism is a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.<ref>PMID:24501278</ref> A KCND2 mutation leading to the production of a C-terminally truncated protein has been identified in a patient with epilepsy. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.<ref>PMID:16934482</ref>	+	[https://www.uniprot.org/uniprot/KCND2_HUMAN KCND2_HUMAN] KNCD2 mutations have been found in a family with autism and epilepsy and may play a role in disease pathogenesis. Autism is a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.<ref>PMID:24501278</ref> A KCND2 mutation leading to the production of a C-terminally truncated protein has been identified in a patient with epilepsy. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.<ref>PMID:16934482</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/KCND2_HUMAN KCND2_HUMAN]] Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:15454437, PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).[UniProtKB:Q63881][UniProtKB:Q9Z0V2]<ref>PMID:10551270</ref> <ref>PMID:10729221</ref> <ref>PMID:11507158</ref> <ref>PMID:14623880</ref> <ref>PMID:14695263</ref> <ref>PMID:14980201</ref> <ref>PMID:15454437</ref> <ref>PMID:16934482</ref> <ref>PMID:19171772</ref> <ref>PMID:24501278</ref> <ref>PMID:24811166</ref>	+	[https://www.uniprot.org/uniprot/KCND2_HUMAN KCND2_HUMAN] Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:15454437, PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).[UniProtKB:Q63881][UniProtKB:Q9Z0V2]<ref>PMID:10551270</ref> <ref>PMID:10729221</ref> <ref>PMID:11507158</ref> <ref>PMID:14623880</ref> <ref>PMID:14695263</ref> <ref>PMID:14980201</ref> <ref>PMID:15454437</ref> <ref>PMID:16934482</ref> <ref>PMID:19171772</ref> <ref>PMID:24501278</ref> <ref>PMID:24811166</ref>
		+
		+	==See Also==
		+	*[[Potassium channel 3D structures\|Potassium channel 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:31, 8 September 2022

2022-09-08T05:31:43Z

←Older revision		Revision as of 05:31, 8 September 2022
Line 3:		Line 3:
	<StructureSection load='7ukf' size='340' side='right'caption='[[7ukf]], [[Resolution\|resolution]] 3.02Å' scene=''>		<StructureSection load='7ukf' size='340' side='right'caption='[[7ukf]], [[Resolution\|resolution]] 3.02Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7ukf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UKF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7ukf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UKF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ukf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ukf OCA], [https://pdbe.org/7ukf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ukf RCSB], [https://www.ebi.ac.uk/pdbsum/7ukf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ukf ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ukf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ukf OCA], [https://pdbe.org/7ukf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ukf RCSB], [https://www.ebi.ac.uk/pdbsum/7ukf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ukf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/KCND2_HUMAN KCND2_HUMAN]] KNCD2 mutations have been found in a family with autism and epilepsy and may play a role in disease pathogenesis. Autism is a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.<ref>PMID:24501278</ref> A KCND2 mutation leading to the production of a C-terminally truncated protein has been identified in a patient with epilepsy. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.<ref>PMID:16934482</ref>	+	[[https://www.uniprot.org/uniprot/KCND2_HUMAN KCND2_HUMAN]] KNCD2 mutations have been found in a family with autism and epilepsy and may play a role in disease pathogenesis. Autism is a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.<ref>PMID:24501278</ref> A KCND2 mutation leading to the production of a C-terminally truncated protein has been identified in a patient with epilepsy. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.<ref>PMID:16934482</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/KCND2_HUMAN KCND2_HUMAN]] Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:15454437, PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).[UniProtKB:Q63881][UniProtKB:Q9Z0V2]<ref>PMID:10551270</ref> <ref>PMID:10729221</ref> <ref>PMID:11507158</ref> <ref>PMID:14623880</ref> <ref>PMID:14695263</ref> <ref>PMID:14980201</ref> <ref>PMID:15454437</ref> <ref>PMID:16934482</ref> <ref>PMID:19171772</ref> <ref>PMID:24501278</ref> <ref>PMID:24811166</ref>	+	[[https://www.uniprot.org/uniprot/KCND2_HUMAN KCND2_HUMAN]] Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:15454437, PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).[UniProtKB:Q63881][UniProtKB:Q9Z0V2]<ref>PMID:10551270</ref> <ref>PMID:10729221</ref> <ref>PMID:11507158</ref> <ref>PMID:14623880</ref> <ref>PMID:14695263</ref> <ref>PMID:14980201</ref> <ref>PMID:15454437</ref> <ref>PMID:16934482</ref> <ref>PMID:19171772</ref> <ref>PMID:24501278</ref> <ref>PMID:24811166</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The voltage-gated ion channel activity depends on both activation (transition from the resting state to the open state) and inactivation. Inactivation is a self-restraint mechanism to limit ion conduction and is as crucial to membrane excitability as activation. Inactivation can occur when the channel is open or closed. Although open-state inactivation is well understood, the molecular basis of closed-state inactivation has remained elusive. We report cryo-EM structures of human KV4.2 channel complexes in inactivated, open, and closed states. Closed-state inactivation of KV4 involves an unprecedented symmetry breakdown for pore closure by only two of the four S4-S5 linkers, distinct from known mechanisms of open-state inactivation. We further capture KV4 in a putative resting state, revealing how voltage sensor movements control the pore. Moreover, our structures provide insights regarding channel modulation by KChIP2 and DPP6 auxiliary subunits. Our findings elucidate mechanisms of closed-state inactivation and voltage-dependent activation of the KV4 channel.	+
-		+
-	Activation and closed-state inactivation mechanisms of the human voltage-gated KV4 channel complexes.,Ye W, Zhao H, Dai Y, Wang Y, Lo YH, Jan LY, Lee CH Mol Cell. 2022 Jul 7;82(13):2427-2442.e4. doi: 10.1016/j.molcel.2022.04.032. Epub, 2022 May 20. PMID:35597238<ref>PMID:35597238</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 7ukf" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Dai, Y]]	+	[[Category: Dai Y]]
-	[[Category: Lee~~, C H~~]]	+	[[Category: Lee CH]]
-	[[Category: Zhao, H]]	+	[[Category: Zhao H]]
-	~~[[Category: Membrane protein]]~~	+
-	~~[[Category: Potassium channel complex~~]]	+

OCA at 07:16, 20 July 2022

2022-07-20T07:16:09Z

←Older revision		Revision as of 07:16, 20 July 2022
Line 1:		Line 1:

-	==n/a==	+	==Human Kv4.2-KChIP2 channel complex in a putative resting state, transmembrane region==
-	<StructureSection load='7ukf' size='340' side='right'caption='[[7ukf]]' scene=''>	+	<StructureSection load='7ukf' size='340' side='right'caption='[[7ukf]], [[Resolution\|resolution]] 3.02Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UKF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7ukf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UKF FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ukf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ukf OCA], [https://pdbe.org/7ukf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ukf RCSB], [https://www.ebi.ac.uk/pdbsum/7ukf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ukf ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ukf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ukf OCA], [https://pdbe.org/7ukf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ukf RCSB], [https://www.ebi.ac.uk/pdbsum/7ukf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ukf ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/KCND2_HUMAN KCND2_HUMAN]] KNCD2 mutations have been found in a family with autism and epilepsy and may play a role in disease pathogenesis. Autism is a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.<ref>PMID:24501278</ref> A KCND2 mutation leading to the production of a C-terminally truncated protein has been identified in a patient with epilepsy. Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system.<ref>PMID:16934482</ref>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/KCND2_HUMAN KCND2_HUMAN]] Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:15454437, PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).[UniProtKB:Q63881][UniProtKB:Q9Z0V2]<ref>PMID:10551270</ref> <ref>PMID:10729221</ref> <ref>PMID:11507158</ref> <ref>PMID:14623880</ref> <ref>PMID:14695263</ref> <ref>PMID:14980201</ref> <ref>PMID:15454437</ref> <ref>PMID:16934482</ref> <ref>PMID:19171772</ref> <ref>PMID:24501278</ref> <ref>PMID:24811166</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The voltage-gated ion channel activity depends on both activation (transition from the resting state to the open state) and inactivation. Inactivation is a self-restraint mechanism to limit ion conduction and is as crucial to membrane excitability as activation. Inactivation can occur when the channel is open or closed. Although open-state inactivation is well understood, the molecular basis of closed-state inactivation has remained elusive. We report cryo-EM structures of human KV4.2 channel complexes in inactivated, open, and closed states. Closed-state inactivation of KV4 involves an unprecedented symmetry breakdown for pore closure by only two of the four S4-S5 linkers, distinct from known mechanisms of open-state inactivation. We further capture KV4 in a putative resting state, revealing how voltage sensor movements control the pore. Moreover, our structures provide insights regarding channel modulation by KChIP2 and DPP6 auxiliary subunits. Our findings elucidate mechanisms of closed-state inactivation and voltage-dependent activation of the KV4 channel.
		+
		+	Activation and closed-state inactivation mechanisms of the human voltage-gated KV4 channel complexes.,Ye W, Zhao H, Dai Y, Wang Y, Lo YH, Jan LY, Lee CH Mol Cell. 2022 Jul 7;82(13):2427-2442.e4. doi: 10.1016/j.molcel.2022.04.032. Epub, 2022 May 20. PMID:35597238<ref>PMID:35597238</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7ukf" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~N/a~~]]	+	[[Category: Dai, Y]]
		+	[[Category: Lee, C H]]
		+	[[Category: Zhao, H]]
		+	[[Category: Membrane protein]]
		+	[[Category: Potassium channel complex]]

OCA at 07:28, 29 June 2022

2022-06-29T07:28:01Z

←Older revision		Revision as of 07:28, 29 June 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7ukf ~~is ON HOLD until Paper Publication~~	+	==n/a==
-		+	<StructureSection load='7ukf' size='340' side='right'caption='[[7ukf]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UKF FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ukf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ukf OCA], [https://pdbe.org/7ukf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ukf RCSB], [https://www.ebi.ac.uk/pdbsum/7ukf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ukf ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: N/a]]

OCA at 04:44, 12 May 2022

2022-05-12T04:44:27Z

←Older revision		Revision as of 04:44, 12 May 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7ukf is ON HOLD	+	The entry 7ukf is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7ukf" [edit=sysop:move=sysop]

2022-04-06T09:09:26Z

Protected "7ukf" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:09, 6 April 2022

OCA: New page: '''Unreleased structure''' The entry 7ukf is ON HOLD Authors: Description: Category: Unreleased Structures

2022-04-06T09:09:25Z

New page: '''Unreleased structure''' The entry 7ukf is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7ukf is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]