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| | ==Structure of CALM (PICALM) in complex with VAMP8== | | ==Structure of CALM (PICALM) in complex with VAMP8== |
| - | <StructureSection load='3zym' size='340' side='right' caption='[[3zym]], [[Resolution|resolution]] 2.03Å' scene=''> | + | <StructureSection load='3zym' size='340' side='right'caption='[[3zym]], [[Resolution|resolution]] 2.03Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zym]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZYM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZYM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zym]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZYM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.03Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zyl|3zyl]], [[1hg2|1hg2]], [[1hg5|1hg5]], [[1hfa|1hfa]], [[3zyk|3zyk]], [[1hf8|1hf8]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=3zym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zym OCA], [http://pdbe.org/3zym PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zym RCSB], [http://www.ebi.ac.uk/pdbsum/3zym PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zym 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=3zym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zym OCA], [https://pdbe.org/3zym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zym RCSB], [https://www.ebi.ac.uk/pdbsum/3zym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zym ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PICA_RAT PICA_RAT]] Assembly protein recruiting clathrin and adaptor protein complex 2 (AP2) to cell membranes at sites of coated-pit formation and clathrin-vesicle assembly. May be required to determine the amount of membrane to be recycled, possibly by regulating the size of the clathrin cage. Involved in AP2-dependent clathrin-mediated endocytosis at the neuromuscular junction (By similarity).[UniProtKB:Q13492] | + | [https://www.uniprot.org/uniprot/PICAL_RAT PICAL_RAT] Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly. Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8. In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors. Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF).[UniProtKB:Q13492]<ref>PMID:11190274</ref> [https://www.uniprot.org/uniprot/VAMP8_MOUSE VAMP8_MOUSE] SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane via its interaction with the STX17-SNAP29 binary t-SNARE complex (By similarity). Also required for dense-granule secretion in platelets (By similarity). Also plays a role in regulated enzyme secretion in pancreatic acinar cells (PubMed:15363411). Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells (By similarity). Involved in the homotypic fusion of early and late endosomes (By similarity). Participates also in the activation of type I interferon antiviral response through a TRIM6-dependent mechanism (By similarity).[UniProtKB:Q9BV40]<ref>PMID:15363411</ref> <ref>PMID:22118466</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Graham, S C]] | + | [[Category: Mus musculus]] |
| - | [[Category: Honing, S]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Miller, S E]] | + | [[Category: Graham SC]] |
| - | [[Category: Owen, D J]] | + | [[Category: Honing S]] |
| - | [[Category: Peden, A A]]
| + | [[Category: Miller SE]] |
| - | [[Category: Robinson, M S]]
| + | [[Category: Owen DJ]] |
| - | [[Category: Sahlender, D A]] | + | [[Category: Peden AA]] |
| - | [[Category: Adaptor protein]] | + | [[Category: Robinson MS]] |
| - | [[Category: Ap180]] | + | [[Category: Sahlender DA]] |
| - | [[Category: Endocytosis]] | + | |
| - | [[Category: Plasma membrane]] | + | |
| - | [[Category: Synaptobrevin]]
| + | |
| - | [[Category: Vamp2]]
| + | |
| - | [[Category: Vamp3]]
| + | |
| Structural highlights
Function
PICAL_RAT Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly. Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8. In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors. Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF).[UniProtKB:Q13492][1] VAMP8_MOUSE SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane via its interaction with the STX17-SNAP29 binary t-SNARE complex (By similarity). Also required for dense-granule secretion in platelets (By similarity). Also plays a role in regulated enzyme secretion in pancreatic acinar cells (PubMed:15363411). Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells (By similarity). Involved in the homotypic fusion of early and late endosomes (By similarity). Participates also in the activation of type I interferon antiviral response through a TRIM6-dependent mechanism (By similarity).[UniProtKB:Q9BV40][2] [3]
Publication Abstract from PubMed
SNAREs provide a large part of the specificity and energy needed for membrane fusion and, to do so, must be localized to their correct membranes. Here, we show that the R-SNAREs VAMP8, VAMP3, and VAMP2, which cycle between the plasma membrane and endosomes, bind directly to the ubiquitously expressed, PtdIns4,5P(2)-binding, endocytic clathrin adaptor CALM/PICALM. X-ray crystallography shows that the N-terminal halves of their SNARE motifs bind the CALM(ANTH) domain as helices in a manner that mimics SNARE complex formation. Mutation of residues in the CALM:SNARE interface inhibits binding in vitro and prevents R-SNARE endocytosis in vivo. Thus, CALM:R-SNARE interactions ensure that R-SNAREs, required for the fusion of endocytic clathrin-coated vesicles with endosomes and also for subsequent postendosomal trafficking, are sorted into endocytic vesicles. CALM's role in directing the endocytosis of small R-SNAREs may provide insight into the association of CALM/PICALM mutations with growth retardation, cognitive defects, and Alzheimer's disease.
The Molecular Basis for the Endocytosis of Small R-SNAREs by the Clathrin Adaptor CALM.,Miller SE, Sahlender DA, Graham SC, Honing S, Robinson MS, Peden AA, Owen DJ Cell. 2011 Nov 23;147(5):1118-31. PMID:22118466[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kim HL, Kim JA. Purification of clathrin assembly protein from rat liver. Exp Mol Med. 2000 Dec 31;32(4):222-6. PMID:11190274 doi:10.1038/emm.2000.36
- ↑ Wang CC, Ng CP, Lu L, Atlashkin V, Zhang W, Seet LF, Hong W. A role of VAMP8/endobrevin in regulated exocytosis of pancreatic acinar cells. Dev Cell. 2004 Sep;7(3):359-71. PMID:15363411 doi:10.1016/j.devcel.2004.08.002
- ↑ Miller SE, Sahlender DA, Graham SC, Honing S, Robinson MS, Peden AA, Owen DJ. The Molecular Basis for the Endocytosis of Small R-SNAREs by the Clathrin Adaptor CALM. Cell. 2011 Nov 23;147(5):1118-31. PMID:22118466 doi:10.1016/j.cell.2011.10.038
- ↑ Miller SE, Sahlender DA, Graham SC, Honing S, Robinson MS, Peden AA, Owen DJ. The Molecular Basis for the Endocytosis of Small R-SNAREs by the Clathrin Adaptor CALM. Cell. 2011 Nov 23;147(5):1118-31. PMID:22118466 doi:10.1016/j.cell.2011.10.038
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