6m1i - Revision history

OCA at 07:18, 27 May 2020

OCA — Wed, 27 May 2020 07:18:06 GMT

←Older revision		Revision as of 07:18, 27 May 2020
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	<StructureSection load='6m1i' size='340' side='right'caption='[[6m1i]], [[Resolution\|resolution]] 3.50Å' scene=''>		<StructureSection load='6m1i' size='340' side='right'caption='[[6m1i]], [[Resolution\|resolution]] 3.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6m1i]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M1I OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6M1I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6m1i]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M1I OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6M1I FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6m1h\|6m1h]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6m1h\|6m1h]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6m1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m1i OCA], [http://pdbe.org/6m1i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6m1i RCSB], [http://www.ebi.ac.uk/pdbsum/6m1i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6m1i ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6m1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m1i OCA], [http://pdbe.org/6m1i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6m1i RCSB], [http://www.ebi.ac.uk/pdbsum/6m1i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6m1i ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Camelus glama]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Ma, Y]]		[[Category: Ma, Y]]

OCA at 07:21, 11 March 2020

OCA — Wed, 11 Mar 2020 07:21:51 GMT

←Older revision		Revision as of 07:21, 11 March 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6m1i is ~~ON HOLD~~	+	==CryoEM structure of human PAC1 receptor in complex with PACAP38==
		+	<StructureSection load='6m1i' size='340' side='right'caption='[[6m1i]], [[Resolution\|resolution]] 3.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6m1i]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M1I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6M1I FirstGlance]. <br>
		+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6m1h\|6m1h]]</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6m1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m1i OCA], [http://pdbe.org/6m1i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6m1i RCSB], [http://www.ebi.ac.uk/pdbsum/6m1i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6m1i ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GBG2_HUMAN GBG2_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity). [[http://www.uniprot.org/uniprot/PACA_HUMAN PACA_HUMAN]] Binding to its receptor activates G proteins and stimulates adenylate cyclase in pituitary cells.<ref>PMID:11175907</ref> [[http://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1R) belongs to the secretin receptor family and is widely distributed in the central neural system and peripheral organs. Abnormal activation of the receptor mediates trigeminovascular activation and sensitization, which is highly related to migraine, making PAC1R a potential therapeutic target. Elucidation of PAC1R activation mechanism would benefit discovery of therapeutic drugs for neuronal disorders. PAC1R activity is governed by pituitary adenylate cyclase-activating polypeptide (PACAP), known as a major vasodilator neuropeptide, and maxadilan, a native peptide from the sand fly, which is also capable of activating the receptor with similar potency. These peptide ligands have divergent sequences yet initiate convergent PAC1R activity. It is of interest to understand the mechanism of PAC1R ligand recognition and receptor activity regulation through structural biology. Here we report two near-atomic resolution cryo-EM structures of PAC1R activated by PACAP38 or maxadilan, providing structural insights into two distinct ligand binding modes. The structures illustrate flexibility of the extracellular domain (ECD) for ligands with distinct conformations, where ECD accommodates ligands in different orientations while extracellular loop 1 (ECL1) protrudes to further anchor the ligand bound in the orthosteric site. By structure-guided molecular modeling and mutagenesis, we tested residues in the ligand-binding pockets and identified clusters of residues that are critical for receptor activity. The structures reported here for the first time elucidate the mechanism of specificity and flexibility of ligand recognition and binding for PAC1R, and provide insights toward the design of therapeutic molecules targeting PAC1R.

-	~~Authors: Song, X~~., Wang, J., ~~Zhang~~, D., ~~Wang~~, H.W., Ma, Y.	+	Cryo-EM structures of PAC1 receptor reveal ligand binding mechanism.,Wang J, Song X, Zhang D, Chen X, Li X, Sun Y, Li C, Song Y, Ding Y, Ren R, Harrington EH, Hu LA, Zhong W, Xu C, Huang X, Wang HW, Ma Y Cell Res. 2020 Feb 11. pii: 10.1038/s41422-020-0280-2. doi:, 10.1038/s41422-020-0280-2. PMID:32047270<ref>PMID:32047270</ref>

-	~~Description: CryoEM structure~~ of ~~human PAC1 receptor in complex with PACAP38~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Song, X]]~~	+	<div class="pdbe-citations 6m1i" style="background-color:#fffaf0;"></div>
-	~~[[Category: Wang, H.W]]~~	+	== References ==
-	[[Category: ~~Zhang, D~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Ma, Y]]		[[Category: Ma, Y]]
		+	[[Category: Song, X]]
		+	[[Category: Wang, H W]]
	[[Category: Wang, J]]		[[Category: Wang, J]]
		+	[[Category: Zhang, D]]
		+	[[Category: Gpcr]]
		+	[[Category: Protein binding]]

OCA: Protected "6m1i" [edit=sysop:move=sysop]

OCA — Wed, 04 Mar 2020 05:29:52 GMT

Protected "6m1i" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:29, 4 March 2020

OCA: New page: '''Unreleased structure''' The entry 6m1i is ON HOLD Authors: Song, X., Wang, J., Zhang, D., Wang, H.W., Ma, Y. Description: CryoEM structure of human PAC1 receptor in complex with PAC...

OCA — Wed, 04 Mar 2020 05:29:51 GMT

New page: '''Unreleased structure''' The entry 6m1i is ON HOLD Authors: Song, X., Wang, J., Zhang, D., Wang, H.W., Ma, Y. Description: CryoEM structure of human PAC1 receptor in complex with PAC...

New page

'''Unreleased structure'''

The entry 6m1i is ON HOLD

Authors: Song, X., Wang, J., Zhang, D., Wang, H.W., Ma, Y.

Description: CryoEM structure of human PAC1 receptor in complex with PACAP38
[[Category: Unreleased Structures]]
[[Category: Song, X]]
[[Category: Wang, H.W]]
[[Category: Zhang, D]]
[[Category: Ma, Y]]
[[Category: Wang, J]]