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| | ==Structure of a truncated CALM (PICALM) ANTH domain== | | ==Structure of a truncated CALM (PICALM) ANTH domain== |
| - | <StructureSection load='3zyl' size='340' side='right' caption='[[3zyl]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='3zyl' size='340' side='right'caption='[[3zyl]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zyl]] is a 2 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=3ZYL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZYL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zyl]] is a 2 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=3ZYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZYL FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hg2|1hg2]], [[1hfa|1hfa]], [[1hg5|1hg5]], [[1hf8|1hf8]], [[3zym|3zym]], [[3zyk|3zyk]]</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]] 1.7Å</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=3zyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zyl OCA], [http://pdbe.org/3zyl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zyl RCSB], [http://www.ebi.ac.uk/pdbsum/3zyl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zyl 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=3zyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zyl OCA], [https://pdbe.org/3zyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zyl RCSB], [https://www.ebi.ac.uk/pdbsum/3zyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zyl 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> |
| | <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: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Graham, S C]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Honing, S]] | + | [[Category: Graham SC]] |
| - | [[Category: Miller, S E]] | + | [[Category: Honing S]] |
| - | [[Category: Owen, D J]] | + | [[Category: Miller SE]] |
| - | [[Category: Peden, A A]] | + | [[Category: Owen DJ]] |
| - | [[Category: Robinson, M S]] | + | [[Category: Peden AA]] |
| - | [[Category: Sahlender, D A]] | + | [[Category: Robinson MS]] |
| - | [[Category: Adaptor protein]]
| + | [[Category: Sahlender DA]] |
| - | [[Category: Ap180]]
| + | |
| - | [[Category: Endobrevin]]
| + | |
| - | [[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]
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[2]
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
- ↑ 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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