4k17 | pdb_00004k17
Crystal Structure of mouse CARMIL residues 1-668
Structural highlights
FunctionCARL1_MOUSE Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments. Prevents F-actin heterodimeric capping protein (CP) activity at the leading edges of migrating cells, and hence generates uncapped barbed ends and enhances actin polymerization, however, seems unable to nucleate filaments (PubMed:16054028). Plays a role in lamellipodial protrusion formations and cell migration (PubMed:16054028).[1] Publication Abstract from PubMedCARMIL is an approximately 1,370-amino-acid cytoskeletal scaffold that has crucial roles in cell motility and tissue development through interactions with cytoskeletal effectors and regulation of capping protein at the leading edge. However, the mechanism of CARMIL leading edge localization is unknown. Here we show that CARMIL interacts directly with the plasma membrane through its amino-terminal region. The crystal structure of CARMIL1-668 reveals that this region harbours a non-canonical pleckstrin homology (PH) domain connected to a 16-leucine-rich repeat domain. Lipid binding is mediated by the PH domain, but is further enhanced by a central helical domain. Small-angle X-ray scattering reveals that the helical domain mediates antiparallel dimerization, properly positioning the PH domains for simultaneous membrane interaction. In cells, deletion of the PH domain impairs leading edge localization. The results support a direct membrane-binding mechanism for CARMIL localization at the leading edge, where it regulates cytoskeletal effectors and motility. CARMIL leading edge localization depends on a non-canonical PH domain and dimerization.,Zwolak A, Yang C, Feeser EA, Michael Ostap E, Svitkina T, Dominguez R Nat Commun. 2013 Sep 27;4:2523. doi: 10.1038/ncomms3523. PMID:24071777[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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