PDBsum entry 1rj2

Signaling protein

PDB id

1rj2

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Contents

			Protein chains

					317 a.a. *

			Waters ×15

* Residue conservation analysis

PDB id:

1rj2

Links

Name:

Signaling protein

Title:

Crystal structure of the dh/ph fragment of dbs without bound gtpase

Structure:

Guanine nucleotide exchange factor dbs [fragment]. Chain: a, d, g, j. Fragment: dh/ph fragment (residues 498-842). Synonym: dbl's big sister. Mcf2 transforming sequence-like protein. Ost oncogene. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: mcf2l, ost. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

3.00Å

R-factor:

0.239

R-free:

0.296

Authors:

D.K.Worthylake,K.L.Rossman,J.Sondek

Key ref:

D.K.Worthylake et al. (2004). Crystal structure of the DH/PH fragment of Dbs without bound GTPase. Structure, 12, 1078-1086. PubMed id: 15274927 DOI: 10.1016/j.str.2004.03.021

Date:

18-Nov-03

Release date:

29-Jun-04

PROCHECK

	Headers

	References

Protein chains

Q64096 (MCF2L_MOUSE) - Guanine nucleotide exchange factor DBS from Mus musculus

Seq: Struc:

Seq: Struc:

Seq: Struc:					1149 a.a. 317 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1016/j.str.2004.03.021	Structure 12:1078-1086 (2004)
PubMed id: 15274927

Crystal structure of the DH/PH fragment of Dbs without bound GTPase.
D.K.Worthylake, K.L.Rossman, J.Sondek.

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.

Selected figure(s)



	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.

Figure was selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21033699

X.Wu, S.Ramachandran, M.C.Lin, R.A.Cerione, and J.W.Erickson (2011).
A minimal Rac activation domain in the unconventional guanine nucleotide exchange factor Dock180.

Biochemistry, 50, 1070-1080.

19670212

T.Cierpicki, J.Bielnicki, M.Zheng, J.Gruszczyk, M.Kasterka, M.Petoukhov, A.Zhang, E.J.Fernandez, D.I.Svergun, U.Derewenda, J.H.Bushweller, and Z.S.Derewenda (2009).
The solution structure and dynamics of the DH-PH module of PDZRhoGEF in isolation and in complex with nucleotide-free RhoA.

Protein Sci, 18, 2067-2079.

19153575

W.Feng, and M.Zhang (2009).
Organization and dynamics of PDZ-domain-related supramodules in the postsynaptic density.

Nat Rev Neurosci, 10, 87-99.

18589439

J.E.Chrencik, A.Brooun, H.Zhang, I.I.Mathews, G.L.Hura, S.A.Foster, J.J.Perry, M.Streiff, P.Ramage, H.Widmer, G.M.Bokoch, J.A.Tainer, G.Weckbecker, and P.Kuhn (2008).
Structural basis of guanine nucleotide exchange mediated by the T-cell essential Vav1.

J Mol Biol, 380, 828-843.

PDB code:

3bji

17803212

K.Wiehe, B.Pierce, W.W.Tong, H.Hwang, J.Mintseris, and Z.Weng (2007).
The performance of ZDOCK and ZRANK in rounds 6-11 of CAPRI.

Proteins, 69, 719-725.

17391702

M.K.Chhatriwala, L.Betts, D.K.Worthylake, and J.Sondek (2007).
The DH and PH domains of Trio coordinately engage Rho GTPases for their efficient activation.

J Mol Biol, 368, 1307-1320.

PDB code:

2nz8

18034889

S.G.Jackson, Y.Zhang, R.J.Haslam, and M.S.Junop (2007).
Structural analysis of the carboxy terminal PH domain of pleckstrin bound to D-myo-inositol 1,2,3,5,6-pentakisphosphate.

BMC Struct Biol, 7, 80.

PDB codes:

2i5c 2i5f

18096806

S.Lutz, A.Shankaranarayanan, C.Coco, M.Ridilla, M.R.Nance, C.Vettel, D.Baltus, C.R.Evelyn, R.R.Neubig, T.Wieland, and J.J.Tesmer (2007).
Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs.

Science, 318, 1923-1927.

PDB code:

2rgn

15688002

K.L.Rossman, C.J.Der, and J.Sondek (2005).
GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors.

Nat Rev Mol Cell Biol, 6, 167-180.

15817389

K.L.Rossman, and J.Sondek (2005).
Larger than Dbl: new structural insights into RhoA activation.

Trends Biochem Sci, 30, 163-165.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.