3ZYM

Structure of CALM (PICALM) in complex with VAMP8

Summary for 3ZYM

• Entry DOI: 10.2210/pdb3zym/pdb
• Related: 1HF8 1HFA 1HG2 1HG5 3ZYK 3ZYL
• Descriptor: PHOSPHATIDYLINOSITOL-BINDING CLATHRIN ASSEMBLY PROTEIN, VESICLE-ASSOCIATED MEMBRANE PROTEIN 8, GLYCEROL, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: endocytosis, synaptobrevin, vamp2, vamp3, ap180, plasma membrane, adaptor protein
• Biological source: RATTUS NORVEGICUS (NORWAY RAT); More
• Total number of polymer chains: 3
• Total formula weight: 106593.40

Authors

Miller, S.E.,Sahlender, D.A.,Graham, S.C.,Honing, S.,Robinson, M.S.,Peden, A.A.,Owen, D.J. (deposition date: 2011-08-23, release date: 2011-12-07, Last modification date: 2023-12-20)

Primary citation

Miller, S.E.,Sahlender, D.A.,Graham, S.C.,Honing, S.,Robinson, M.S.,Peden, A.A.,Owen, D.J.
The molecular basis for the endocytosis of small R-SNAREs by the clathrin adaptor CALM.
Cell, 147:1118-1131, 2011

PubMed Abstract: 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.

PubMed: 22118466
DOI: 10.1016/j.cell.2011.10.038

Experimental method

X-RAY DIFFRACTION (2.03 Å)