Structural highlights
Function
[LR16A_MOUSE] Binds CAPZA2 with high affinity and significantly decreases CAPZA2 affinity for actin barbed ends. Increases the rate of elongation from seeds in the presence of CAPZA2, however, seems unable to nucleate filaments. Rapidly uncaps barbed ends capped by CAPZA2 and enhances barbed-end actin polymerization.[1]
Publication Abstract from PubMed
CARMIL 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
- ↑ Yang C, Pring M, Wear MA, Huang M, Cooper JA, Svitkina TM, Zigmond SH. Mammalian CARMIL inhibits actin filament capping by capping protein. Dev Cell. 2005 Aug;9(2):209-21. PMID:16054028 doi:http://dx.doi.org/10.1016/j.devcel.2005.06.008
- ↑ Zwolak A, Yang C, Feeser EA, Michael Ostap E, Svitkina T, Dominguez R. CARMIL leading edge localization depends on a non-canonical PH domain and dimerization. Nat Commun. 2013 Sep 27;4:2523. doi: 10.1038/ncomms3523. PMID:24071777 doi:http://dx.doi.org/10.1038/ncomms3523
