View source for 3zyk


==Structure of CALM (PICALM) ANTH domain==
<StructureSection load='3zyk' size='340' side='right'caption='[[3zyk]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zyk]] 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=3ZYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZYK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</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=3zyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zyk OCA], [https://pdbe.org/3zyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zyk RCSB], [https://www.ebi.ac.uk/pdbsum/3zyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zyk ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== 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<ref>PMID:22118466</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3zyk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Graham SC]]
[[Category: Honing S]]
[[Category: Miller SE]]
[[Category: Owen DJ]]
[[Category: Peden AA]]
[[Category: Robinson MS]]
[[Category: Sahlender DA]]