4K17

Crystal Structure of mouse CARMIL residues 1-668

Summary for 4K17

• Entry DOI: 10.2210/pdb4k17/pdb
• Descriptor: Leucine-rich repeat-containing protein 16A, salicylamide, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: ph domain, lrr domain, lipid binding, protein-protein interaction, phosphatidylserine, phosphatidylinositol, phosphatidylinositol-5-phosphate, plasma membrane, lipid binding protein
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm: Q6EDY6
• Total number of polymer chains: 4
• Total formula weight: 299388.52

Authors

Zwolak, A.,Dominguez, R. (deposition date: 2013-04-04, release date: 2013-10-09, Last modification date: 2024-11-27)

Primary citation

Zwolak, A.,Yang, C.,Feeser, E.A.,Michael Ostap, E.,Svitkina, T.,Dominguez, R.
CARMIL leading edge localization depends on a non-canonical PH domain and dimerization.
Nat Commun, 4:2523-2523, 2013

PubMed Abstract: 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.

PubMed: 24071777
DOI: 10.1038/ncomms3523

Experimental method

X-RAY DIFFRACTION (2.895 Å)