6a68: Difference between revisions

Latest revision as of 09:41, 23 October 2024

the crystal structure of rat calcium-dependent activator protein for secretion (CAPS) DAMH domain

Structural highlights

6a68 is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.901Å
Ligands:	K, MSE
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CAPS1_RAT Calcium-binding protein involved in exocytosis of vesicles filled with neurotransmitters and neuropeptides. Probably acts upstream of fusion in the biogenesis or maintenance of mature secretory vesicles. Regulates catecholamine loading of DCVs. May specifically mediate the Ca(2+)-dependent exocytosis of large dense-core vesicles (DCVs) and other dense-core vesicles by acting as a PtdIns(4,5)P2-binding protein that acts at prefusion step following ATP-dependent priming and participates in DCVs-membrane fusion. However, it may also participate in small clear synaptic vesicles (SVs) exocytosis and it is unclear whether its function is related to Ca(2+) triggering.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Exocytosis of synaptic vesicles and dense-core vesicles requires both the Munc13 and CAPS (Ca(2+)-dependent activator proteins for secretion) proteins. CAPS contains a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-binding region (called the DAMH domain), which has been found to be essential for SNARE-mediated exocytosis. Here we report a crystal structure of the CAPS-1 DAMH domain at 2.9-A resolution and reveal a dual role of CAPS-1 in SNARE complex formation. CAPS-1 plays an inhibitory role dependent on binding of the DAMH domain to the MUN domain of Munc13-1, which hinders the ability of Munc13 to catalyze opening of syntaxin-1, inhibiting SNARE complex formation, and a chaperone role dependent on interaction of the DAMH domain with the syntaxin-1/SNAP-25 complex, which stabilizes the open conformation of Syx1, facilitating SNARE complex formation. Our results suggest that CAPS-1 facilitates SNARE complex formation via the DAMH domain in a manner dependent on sequential and cooperative interaction with Munc13-1 and SNARE proteins.

Structural and Functional Analysis of the CAPS SNARE-Binding Domain Required for SNARE Complex Formation and Exocytosis.,Zhou H, Wei Z, Wang S, Yao D, Zhang R, Ma C Cell Rep. 2019 Mar 19;26(12):3347-3359.e6. doi: 10.1016/j.celrep.2019.02.064. PMID:30893606^[7]

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

References

↑ Rupnik M, Kreft M, Sikdar SK, Grilc S, Romih R, Zupancic G, Martin TF, Zorec R. Rapid regulated dense-core vesicle exocytosis requires the CAPS protein. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5627-32. PMID:10792045 doi:https://dx.doi.org/10.1073/pnas.090359097
↑ Walent JH, Porter BW, Martin TF. A novel 145 kd brain cytosolic protein reconstitutes Ca(2+)-regulated secretion in permeable neuroendocrine cells. Cell. 1992 Sep 4;70(5):765-75. PMID:1516133
↑ Grishanin RN, Kowalchyk JA, Klenchin VA, Ann K, Earles CA, Chapman ER, Gerona RR, Martin TF. CAPS acts at a prefusion step in dense-core vesicle exocytosis as a PIP2 binding protein. Neuron. 2004 Aug 19;43(4):551-62. PMID:15312653 doi:https://dx.doi.org/10.1016/j.neuron.2004.07.028
↑ Martin TF, Kowalchyk JA. Docked secretory vesicles undergo Ca2+-activated exocytosis in a cell-free system. J Biol Chem. 1997 May 30;272(22):14447-53. PMID:9162085
↑ Berwin B, Floor E, Martin TF. CAPS (mammalian UNC-31) protein localizes to membranes involved in dense-core vesicle exocytosis. Neuron. 1998 Jul;21(1):137-45. PMID:9697858
↑ Tandon A, Bannykh S, Kowalchyk JA, Banerjee A, Martin TF, Balch WE. Differential regulation of exocytosis by calcium and CAPS in semi-intact synaptosomes. Neuron. 1998 Jul;21(1):147-54. PMID:9697859
↑ Zhou H, Wei Z, Wang S, Yao D, Zhang R, Ma C. Structural and Functional Analysis of the CAPS SNARE-Binding Domain Required for SNARE Complex Formation and Exocytosis. Cell Rep. 2019 Mar 19;26(12):3347-3359.e6. doi: 10.1016/j.celrep.2019.02.064. PMID:30893606 doi:https://dx.doi.org/10.1016/j.celrep.2019.02.064

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OCA

[1] Rupnik M, Kreft M, Sikdar SK, Grilc S, Romih R, Zupancic G, Martin TF, Zorec R. Rapid regulated dense-core vesicle exocytosis requires the CAPS protein. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5627-32. PMID:10792045 doi:https://dx.doi.org/10.1073/pnas.090359097

[2] Walent JH, Porter BW, Martin TF. A novel 145 kd brain cytosolic protein reconstitutes Ca(2+)-regulated secretion in permeable neuroendocrine cells. Cell. 1992 Sep 4;70(5):765-75. PMID:1516133

[3] Grishanin RN, Kowalchyk JA, Klenchin VA, Ann K, Earles CA, Chapman ER, Gerona RR, Martin TF. CAPS acts at a prefusion step in dense-core vesicle exocytosis as a PIP2 binding protein. Neuron. 2004 Aug 19;43(4):551-62. PMID:15312653 doi:https://dx.doi.org/10.1016/j.neuron.2004.07.028

[4] Martin TF, Kowalchyk JA. Docked secretory vesicles undergo Ca2+-activated exocytosis in a cell-free system. J Biol Chem. 1997 May 30;272(22):14447-53. PMID:9162085

[5] Berwin B, Floor E, Martin TF. CAPS (mammalian UNC-31) protein localizes to membranes involved in dense-core vesicle exocytosis. Neuron. 1998 Jul;21(1):137-45. PMID:9697858

[6] Tandon A, Bannykh S, Kowalchyk JA, Banerjee A, Martin TF, Balch WE. Differential regulation of exocytosis by calcium and CAPS in semi-intact synaptosomes. Neuron. 1998 Jul;21(1):147-54. PMID:9697859

[7] Zhou H, Wei Z, Wang S, Yao D, Zhang R, Ma C. Structural and Functional Analysis of the CAPS SNARE-Binding Domain Required for SNARE Complex Formation and Exocytosis. Cell Rep. 2019 Mar 19;26(12):3347-3359.e6. doi: 10.1016/j.celrep.2019.02.064. PMID:30893606 doi:https://dx.doi.org/10.1016/j.celrep.2019.02.064

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@@ Line 3: / Line 3: @@
 <StructureSection load='6a68' size='340' side='right'caption='[[6a68]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6a68]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A68 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A68 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6a68]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A68 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A68 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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">X-ray diffraction, [[Resolution|Resolution]] 2.901&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cadps, Caps, Caps1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=6a68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a68 OCA], [https://pdbe.org/6a68 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a68 RCSB], [https://www.ebi.ac.uk/pdbsum/6a68 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a68 ProSAT]</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=6a68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a68 OCA], [http://pdbe.org/6a68 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a68 RCSB], [http://www.ebi.ac.uk/pdbsum/6a68 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a68 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CAPS1_RAT CAPS1_RAT]] Calcium-binding protein involved in exocytosis of vesicles filled with neurotransmitters and neuropeptides. Probably acts upstream of fusion in the biogenesis or maintenance of mature secretory vesicles. Regulates catecholamine loading of DCVs. May specifically mediate the Ca(2+)-dependent exocytosis of large dense-core vesicles (DCVs) and other dense-core vesicles by acting as a PtdIns(4,5)P2-binding protein that acts at prefusion step following ATP-dependent priming and participates in DCVs-membrane fusion. However, it may also participate in small clear synaptic vesicles (SVs) exocytosis and it is unclear whether its function is related to Ca(2+) triggering.<ref>PMID:10792045</ref> <ref>PMID:1516133</ref> <ref>PMID:15312653</ref> <ref>PMID:9162085</ref> <ref>PMID:9697858</ref> <ref>PMID:9697859</ref>
+[https://www.uniprot.org/uniprot/CAPS1_RAT CAPS1_RAT] Calcium-binding protein involved in exocytosis of vesicles filled with neurotransmitters and neuropeptides. Probably acts upstream of fusion in the biogenesis or maintenance of mature secretory vesicles. Regulates catecholamine loading of DCVs. May specifically mediate the Ca(2+)-dependent exocytosis of large dense-core vesicles (DCVs) and other dense-core vesicles by acting as a PtdIns(4,5)P2-binding protein that acts at prefusion step following ATP-dependent priming and participates in DCVs-membrane fusion. However, it may also participate in small clear synaptic vesicles (SVs) exocytosis and it is unclear whether its function is related to Ca(2+) triggering.<ref>PMID:10792045</ref> <ref>PMID:1516133</ref> <ref>PMID:15312653</ref> <ref>PMID:9162085</ref> <ref>PMID:9697858</ref> <ref>PMID:9697859</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Buffalo rat]]
 [[Category: Large Structures]]
-[[Category: Ma, C]]
+[[Category: Rattus norvegicus]]
-[[Category: Wei, Z Q]]
+[[Category: Ma C]]
-[[Category: Yao, D Q]]
+[[Category: Wei ZQ]]
-[[Category: Zhang, R G]]
+[[Category: Yao DQ]]
-[[Category: Zhou, H]]
+[[Category: Zhang RG]]
-[[Category: Exocytosis]]
+[[Category: Zhou H]]
-[[Category: Exocytosis dcv transition]]

6a68: Difference between revisions

Latest revision as of 09:41, 23 October 2024

the crystal structure of rat calcium-dependent activator protein for secretion (CAPS) DAMH domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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