1CEE

SOLUTION STRUCTURE OF CDC42 IN COMPLEX WITH THE GTPASE BINDING DOMAIN OF WASP

Summary for 1CEE

• Entry DOI: 10.2210/pdb1cee/pdb
• Descriptor: GTP-BINDING RHO-LIKE PROTEIN, WISKOTT-ALDRICH SYNDROME PROTEIN WASP, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: cdc42 actin regulator gtpase and the gtpase binding domain of its effector wasp, structural protein regulation
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P60953; Cytoplasm, cytoskeleton: P42768
• Total number of polymer chains: 2
• Total formula weight: 26809.40

Authors

Abdul-Manan, N.,Aghazadeh, B.,Liu, G.A.,Majumdar, A.,Ouerfelli, O.,Rosen, M.K. (deposition date: 1999-03-08, release date: 1999-06-30, Last modification date: 2023-12-27)

Primary citation

Abdul-Manan, N.,Aghazadeh, B.,Liu, G.A.,Majumdar, A.,Ouerfelli, O.,Siminovitch, K.A.,Rosen, M.K.
Structure of Cdc42 in complex with the GTPase-binding domain of the 'Wiskott-Aldrich syndrome' protein.
Nature, 399:379-383, 1999

PubMed Abstract: The Rho-family GTP-hydrolysing proteins (GTPases), Cdc42, Rac and Rho, act as molecular switches in signalling pathways that regulate cytoskeletal architecture, gene expression and progression of the cell cycle. Cdc42 and Rac transmit many signals through GTP-dependent binding to effector proteins containing a Cdc42/Rac-interactive-binding (CRIB) motif. One such effector, the Wiskott-Aldrich syndrome protein (WASP), is postulated to link activation of Cdc42 directly to the rearrangement of actin. Human mutations in WASP cause severe defects in haematopoletic cell function, leading to clinical symptoms of thrombocytopenia, immunodeficiency and eczema. Here we report the solution structure of a complex between activated Cdc42 and a minimal GTPase-binding domain (GBD) from WASP. An extended amino-terminal GBD peptide that includes the CRIB motif contacts the switch I, beta2 and alpha5 regions of Cdc42. A carboxy-terminal beta-hairpin and alpha-helix pack against switch II. The Phe-X-His-X2-His portion of the CRIB motif and the alpha-helix appear to mediate sensitivity to the nucleotide switch through contacts to residues 36-40 of Cdc42. Discrimination between the Rho-family members is likely to be governed by GBD contacts to the switch I and alpha5 regions of the GTPases. Structural and biochemical data suggest that GBD-sequence divergence outside the CRIB motif may reflect additional regulatory interactions with functional domains that are specific to individual effectors.

PubMed: 10360578
DOI: 10.1038/20726

Experimental method

SOLUTION NMR