1LB1

Crystal Structure of the Dbl and Pleckstrin homology domains of Dbs in complex with RhoA

Summary for 1LB1

• Entry DOI: 10.2210/pdb1lb1/pdb
• Related: 1FOE 1KI1 1KZ7 1KZG
• Descriptor: Guanine nucleotide exchange factor DBS, Transforming protein RhoA (2 entities in total)
• Functional Keywords: guanine nucleotide exchange factor, small g-protein, rhoa, dbs, dh domain, ph domain, signaling protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cytoplasm: Q64096; Cell membrane; Lipid-anchor; Cytoplasmic side: P61586
• Total number of polymer chains: 8
• Total formula weight: 251352.43

Authors

Snyder, J.T.,Worthylake, D.K.,Rossman, K.L.,Betts, L.,Pruitt, W.M.,Siderovski, D.P.,Der, C.J.,Sondek, J. (deposition date: 2002-04-01, release date: 2002-05-29, Last modification date: 2023-08-16)

Primary citation

Snyder, J.T.,Worthylake, D.K.,Rossman, K.L.,Betts, L.,Pruitt, W.M.,Siderovski, D.P.,Der, C.J.,Sondek, J.
Structural basis for the selective activation of Rho GTPases by Dbl exchange factors.
Nat.Struct.Biol., 9:468-475, 2002

PubMed Abstract: Activation of Rho-family GTPases involves the removal of bound GDP and the subsequent loading of GTP, all catalyzed by guanine nucleotide exchange factors (GEFs) of the Dbl-family. Despite high sequence conservation among Rho GTPases, Dbl proteins possess a wide spectrum of discriminatory potentials for Rho-family members. To rationalize this specificity, we have determined crystal structures of the conserved, catalytic fragments (Dbl and pleckstrin homology domains) of the exchange factors intersectin and Dbs in complex with their cognate GTPases, Cdc42 and RhoA, respectively. Structure-based mutagenesis of intersectin and Dbs reveals the key determinants responsible for promoting exchange activity in Cdc42, Rac1 and RhoA. These findings provide critical insight into the structural features necessary for the proper pairing of Dbl-exchange factors with Rho GTPases and now allow for the detailed manipulation of signaling pathways mediated by these oncoproteins in vivo.

PubMed: 12006984
DOI: 10.1038/nsb796

Experimental method

X-RAY DIFFRACTION (2.81 Å)