PDBsum entry 1rj2

Signaling protein

PDB id: 1rj2

Contents

Protein chains

317 a.a. *

Waters ×15

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Crystal structure of the dh/ph fragment of dbs without bound gtpase.
• Authors: D.K.Worthylake, K.L.Rossman, J.Sondek.
• Ref.: Structure, 2004, 12, 1078-1086. [DOI no: 10.1016/j.str.2004.03.021]
• PubMed id: 15274927

Abstract

Dbl proteins are guanine nucleotide exchange factors for Rho GTPases, containing adjacent Dbl homology (DH) and pleckstrin homology (PH) domains. This domain architecture is virtually invariant and typically required for full exchange potential. Several structures of DH/PH fragments bound to GTPases implicate the PH domain in nucleotide exchange. To more fully understand the functional linkage between DH and PH domains, we have determined the crystal structure of the DH/PH fragment of Dbs without bound GTPase. This structure is generally similar to previously determined structures of Dbs bound to GTPases albeit with greater apparent mobility between the DH and PH domains. These comparisons suggest that the DH and PH domains of Dbs are spatially primed for binding GTPases and small alterations in intradomain conformations that may be elicited by subtle biological responses, such as altered phosphoinositide levels, are sufficient to enhance exchange by facilitating interactions between the PH domain and GTPases.

Figure 3.
Figure 3. Conformational Changes Induced within the DH/PH Domains of Dbs upon Binding a GTPaseThe structure of Dbs·RhoA (transparent) was superimposed on the GTPase-free form of Dbs (molecule B) using DH domain residues. Significant interactions between RhoA and the b3/b4 loop as well as a6 serve to reduce the conformational heterogeneity between DH and PH domains and result in the ordering of the b3/b4 loop and the tilting of the PH domain toward the GTPase.

The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 1078-1086) copyright 2004.