4N78: The Wave Regulatory Complex Links Diverse Receptors To The Actin Cytoskeleton

The WAVE regulatory complex (WRC) controls actin cytoskeletal dynamics throughout the cell by stimulating the actin-nucleating activity of the Arp2/3 complex at distinct membrane sites. However, the factors that recruit the WRC to specific locations remain poorly understood. Here, we have identified a large family of potential WRC ligands, consisting of approximately 120 diverse membrane proteins, including protocadherins, ROBOs, netrin receptors, neuroligins, GPCRs, and channels. Structural, biochemical, and cellular studies reveal that a sequence motif that defines these ligands binds to a highly conserved interaction surface of the WRC formed by the Sra and Abi subunits. Mutating this binding surface in flies resulted in defects in actin cytoskeletal organization and egg morphology during oogenesis, leading to female sterility. Our findings directly link diverse membrane proteins to the WRC and actin cytoskeleton and have broad physiological and pathological ramifications in metazoans.
PDB ID: 4N78Download
MMDB ID: 117304
PDB Deposition Date: 2013/10/15
Updated in MMDB: 2014/02
Experimental Method:
x-ray diffraction
Resolution: 2.43  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4N78: hexameric; determined by author and by software (PISA)
Molecular Components in 4N78
Label Count Molecule
Proteins (6 molecules)
Cytoplasmic Fmr1-interacting Protein 1(Gene symbol: CYFIP1)
Molecule annotation
Nck-associated Protein 1(Gene symbol: NCKAP1)
Molecule annotation
Wiskott-aldrich Syndrome Protein Family Member 1(Gene symbol: WASF1)
Molecule annotation
Protein Brick1(Gene symbol: BRK1)
Molecule annotation
ABL Interactor 2
Molecule annotation
Molecule annotation
Chemicals (20 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB