5m61 | pdb_00005m61
Clathrin heavy chain N-terminal domain bound to an extended amphiphysin clathrin-box motif
Structural highlights
Function[CLH1_BOVIN] Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. [AMPH_HUMAN] May participate in mechanisms of regulated exocytosis in synapses and certain endocrine cell types. May control the properties of the membrane associated cytoskeleton. Publication Abstract from PubMedShort peptide motifs in unstructured regions of clathrin-adaptor proteins recruit clathrin to membranes to facilitate post-Golgi membrane transport. Three consensus clathrin-binding peptide sequences have been identified and structural studies show that each binds distinct sites on the clathrin heavy chain N-terminal domain (NTD). A fourth binding site for adaptors on NTD has been functionally identified but not structurally characterised. We have solved high resolution structures of NTD bound to peptide motifs from the cellular clathrin adaptors beta2 adaptin and amphiphysin plus a putative viral clathrin adaptor, hepatitis D virus large antigen (HDAg-L). Surprisingly, with each peptide we observe simultaneous peptide binding at multiple sites on NTD and viral peptides binding to the same sites as cellular peptides. Peptides containing clathrin-box motifs (CBMs) with consensus sequence LPhixPhi[DE] bind at the 'arrestin box' on NTD, between beta-propeller blades 4 and 5, which had previously been thought to bind a distinct consensus sequence. Further, we structurally define the fourth peptide binding site on NTD, which we term the Royle box. In vitro binding assays show that clathrin is more readily captured by cellular CBMs than by HDAg-L, and site-directed mutagenesis confirms that multiple binding sites on NTD contribute to efficient capture by CBM peptides. Cellular and viral peptides bind multiple sites on the N-terminal domain of clathrin.,Muenzner J, Traub LM, Kelly BT, Graham SC Traffic. 2016 Nov 3. doi: 10.1111/tra.12457. PMID:27813245[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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