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2vay

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Revision as of 08:49, 12 September 2018

Calmodulin complexed with CaV1.1 IQ peptide

Structural highlights

2vay is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1aji, 1cdl, 1cll, 1iwq, 1j7o, 1j7p, 1l7z, 1pk0, 1s26, 1sw8, 1xfu, 1xfv, 1xfw, 1xfy, 1yr5, 1yru, 1zot, 2v01, 2v02, 1ctr, 1k90, 1k93, 1lvc, 1nkf, 1sk6, 1wrz, 1xfx, 1xfz, 1y6w, 1yrt, 2be6, 2f3y, 2f3z
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CAC1S_HUMAN] Defects in CACNA1S are the cause of periodic paralysis hypokalemic type 1 (HOKPP1) [MIM:170400]; also designated HYPOPP. HOKPP1 is an autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels.^[1] ^[2] ^[3] ^[4] ^[5] Genetic variations in CACNA1S are the cause of susceptibility to malignant hyperthermia 5 (MHS5) [MIM:601887]; an autosomal dominant disorder that is potentially lethal in susceptible individuals on exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants.^[6] Defects in CACNA1S are the cause of susceptibility to thyrotoxic periodic paralysis type 1 (TTPP1) [MIM:188580]. A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease.^[7]

Function

[CAC1S_HUMAN] Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Calmodulin binds to IQ motifs in the alpha(1) subunit of Ca(V)1.1 and Ca(V)1.2, but the affinities of calmodulin for the motif and for Ca(2+) are higher when bound to Ca(V)1.2 IQ. The Ca(V)1.1 IQ and Ca(V)1.2 IQ sequences differ by four amino acids. We determined the structure of calmodulin bound to Ca(V)1.1 IQ and compared it with that of calmodulin bound to Ca(V)1.2 IQ. Four methionines in Ca(2+)-calmodulin form a hydrophobic binding pocket for the peptide, but only one of the four nonconserved amino acids (His-1532 of Ca(V)1.1 and Tyr-1675 of Ca(V)1.2) contacts this calmodulin pocket. However, Tyr-1675 in Ca(V)1.2 contributes only modestly to the higher affinity of this peptide for calmodulin; the other three amino acids in Ca(V)1.2 contribute significantly to the difference in the Ca(2+) affinity of the bound calmodulin despite having no direct contact with calmodulin. Those residues appear to allow an interaction with calmodulin with one lobe Ca(2+)-bound and one lobe Ca(2+)-free. Our data also provide evidence for lobe-lobe interactions in calmodulin bound to Ca(V)1.2.

Determinants in CaV1 channels that regulate the Ca2+ sensitivity of bound calmodulin.,Halling DB, Georgiou DK, Black DJ, Yang G, Fallon JL, Quiocho FA, Pedersen SE, Hamilton SL J Biol Chem. 2009 Jul 24;284(30):20041-51. Epub 2009 May 27. PMID:19473981^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ptacek LJ, Tawil R, Griggs RC, Engel AG, Layzer RB, Kwiecinski H, McManis PG, Santiago L, Moore M, Fouad G, et al.. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell. 1994 Jun 17;77(6):863-8. PMID:8004673
↑ Jurkat-Rott K, Lehmann-Horn F, Elbaz A, Heine R, Gregg RG, Hogan K, Powers PA, Lapie P, Vale-Santos JE, Weissenbach J, et al.. A calcium channel mutation causing hypokalemic periodic paralysis. Hum Mol Genet. 1994 Aug;3(8):1415-9. PMID:7987325
↑ Kim JB, Kim MH, Lee SJ, Kim DJ, Lee BC. The genotype and clinical phenotype of Korean patients with familial hypokalemic periodic paralysis. J Korean Med Sci. 2007 Dec;22(6):946-51. PMID:18162704
↑ Houinato D, Laleye A, Adjien C, Adjagba M, Sternberg D, Hilbert P, Vallat JM, Darboux RB, Funalot B, Avode DG. Hypokalaemic periodic paralysis due to the CACNA1S R1239H mutation in a large African family. Neuromuscul Disord. 2007 May;17(5):419-22. Epub 2007 Apr 5. PMID:17418573 doi:10.1016/j.nmd.2007.01.020
↑ Matthews E, Labrum R, Sweeney MG, Sud R, Haworth A, Chinnery PF, Meola G, Schorge S, Kullmann DM, Davis MB, Hanna MG. Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. Neurology. 2009 May 5;72(18):1544-7. Epub 2008 Dec 31. PMID:19118277 doi:01.wnl.0000342387.65477.46
↑ Monnier N, Procaccio V, Stieglitz P, Lunardi J. Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle. Am J Hum Genet. 1997 Jun;60(6):1316-25. PMID:9199552
↑ Kung AW, Lau KS, Fong GC, Chan V. Association of novel single nucleotide polymorphisms in the calcium channel alpha 1 subunit gene (Ca(v)1.1) and thyrotoxic periodic paralysis. J Clin Endocrinol Metab. 2004 Mar;89(3):1340-5. PMID:15001631
↑ Halling DB, Georgiou DK, Black DJ, Yang G, Fallon JL, Quiocho FA, Pedersen SE, Hamilton SL. Determinants in CaV1 channels that regulate the Ca2+ sensitivity of bound calmodulin. J Biol Chem. 2009 Jul 24;284(30):20041-51. Epub 2009 May 27. PMID:19473981 doi:10.1074/jbc.M109.013326

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vay"

@@ Line 1: / Line 1: @@
-==CALMODULIN COMPLEXED WITH CAV1.1 IQ PEPTIDE==
+==Calmodulin complexed with CaV1.1 IQ peptide==
 <StructureSection load='2vay' size='340' side='right' caption='[[2vay]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
 == Structural highlights ==
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1aji|1aji]], [[1cdl|1cdl]], [[1cll|1cll]], [[1iwq|1iwq]], [[1j7o|1j7o]], [[1j7p|1j7p]], [[1l7z|1l7z]], [[1pk0|1pk0]], [[1s26|1s26]], [[1sw8|1sw8]], [[1xfu|1xfu]], [[1xfv|1xfv]], [[1xfw|1xfw]], [[1xfy|1xfy]], [[1yr5|1yr5]], [[1yru|1yru]], [[1zot|1zot]], [[2v01|2v01]], [[2v02|2v02]], [[1ctr|1ctr]], [[1k90|1k90]], [[1k93|1k93]], [[1lvc|1lvc]], [[1nkf|1nkf]], [[1sk6|1sk6]], [[1wrz|1wrz]], [[1xfx|1xfx]], [[1xfz|1xfz]], [[1y6w|1y6w]], [[1yrt|1yrt]], [[2be6|2be6]], [[2f3y|2f3y]], [[2f3z|2f3z]]</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=2vay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vay OCA], [http://pdbe.org/2vay PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vay RCSB], [http://www.ebi.ac.uk/pdbsum/2vay PDBsum]</span></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=2vay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vay OCA], [http://pdbe.org/2vay PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vay RCSB], [http://www.ebi.ac.uk/pdbsum/2vay PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vay ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/va/2vay_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/va/2vay_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 43: / Line 44: @@
 [[Category: Hamilton, S L]]
 [[Category: Pedersen, S E]]
+[[Category: Acetylation]]
 [[Category: Alpha-1s subunit]]
+[[Category: Calcium]]
 [[Category: Calcium channel]]
 [[Category: Calcium transport]]
@@ Line 58: / Line 61: @@
 [[Category: Transmembrane]]
 [[Category: Transport]]
+[[Category: Ubl conjugation]]
 [[Category: Voltage-dependent]]
 [[Category: Voltage-gated channel]]

2vay

From Proteopedia

Revision as of 08:49, 12 September 2018

Calmodulin complexed with CaV1.1 IQ peptide

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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