PDBsum entry 4k17

Lipid binding protein

PDB id: 4k17

Contents

Protein chains

660 a.a.

Ligands

OHB

ABU

Metals

_CL

PDB id:

4k17

Name:

Lipid binding protein

Title:

Crystal structure of mouse carmil residues 1-668

Structure:

Leucine-rich repeat-containing protein 16a. Chain: a, b, c, d. Fragment: ph and lrr domains (unp residues 1-668). Synonym: carmil1, carmil homolog. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: carmil, lrrc16, lrrc16a. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.90Å R-factor: 0.215 R-free: 0.259

Authors:

A.Zwolak,R.Dominguez

Key ref:

A.Zwolak et al. (2013). CARMIL leading edge localization depends on a non-canonical PH domain and dimerization. Nat Commun, 4, 2523. PubMed id: 24071777 DOI: 10.1038/ncomms3523

Date:

04-Apr-13 Release date: 09-Oct-13

Protein chains

Q6EDY6  (CARL1_MOUSE) -  F-actin-uncapping protein LRRC16A from Mus musculus

Seq: 1374 a.a.

Struc: 660 a.a.

DOI no: 10.1038/ncomms3523

Nat Commun 4:2523 (2013)

PubMed id: 24071777

CARMIL leading edge localization depends on a non-canonical PH domain and dimerization.

A.Zwolak, C.Yang, E.A.Feeser, E.M.Ostap, T.Svitkina, R.Dominguez.

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.