PDBsum entry 6bc0

Signaling protein

PDB id: 6bc0

Contents

Protein chains

131 a.a.

179 a.a.

Ligands

GSP

Metals

_MG

Waters ×47

PDB id:

6bc0

Name:

Signaling protein

Title:

A complex between ph domain of p190rhogef and activated rhoa bound to a gtp analog

Structure:

Rho guanine nucleotide exchange factor 28. Chain: a. Synonym: 190 kda guanine nucleotide exchange factor,p190rhogef,rho guanine nucleotide exchange factor. Engineered: yes. Transforming protein rhoa. Chain: f. Synonym: rho cdna clone 12,h12. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: arhgef28, kiaa1998, rgnef. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: rhoa, arh12, arha, rho12.

Resolution:

2.20Å R-factor: 0.226 R-free: 0.281

Authors:

Z.Chen,P.C.Sternweis

Key ref:

O.Dada et al. (2018). Direct regulation of p190RhoGEF by activated Rho and Rac GTPases. J Struct Biol, 202, 13-24. PubMed id: 29196061 DOI: 10.1016/j.jsb.2017.11.014

Date:

20-Oct-17 Release date: 13-Dec-17

Protein chain

Q8N1W1  (ARG28_HUMAN) -  Rho guanine nucleotide exchange factor 28 from Homo sapiens

Seq: 1705 a.a.

Struc: 131 a.a.

Protein chain

P61586  (RHOA_HUMAN) -  Transforming protein RhoA from Homo sapiens

Seq: 193 a.a.

Struc: 179 a.a.

Enzyme reactions

• Enzyme class 2: Chain A: E.C.?
• Enzyme class 3: Chain F: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

GTP (Bound ligand (Het Group name = GSP) matches with 93.94% similarity) + H2O = GDP + phosphate + H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.jsb.2017.11.014

J Struct Biol 202:13-24 (2018)

PubMed id: 29196061

Direct regulation of p190RhoGEF by activated Rho and Rac GTPases.

O.Dada, S.Gutowski, C.A.Brautigam, Z.Chen, P.C.Sternweis.

ABSTRACT

Rho family GTPases regulate a wide range of cellular processes. This includes cellular dynamics where three subfamilies, Rho, Rac, and Cdc42, are known to regulate cell shape and migration though coordinate action. Activation of Rho proteins largely depends on Rho Guanine nucleotide Exchange Factors (RhoGEFs) through a catalytic Dbl homology (DH) domain linked to a pleckstrin homology (PH) domain that subserves various functions. The PH domains from Lbc RhoGEFs, which specifically activate RhoA, have been shown to bind to activated RhoA. Here, p190RhoGEF is shown to also bind Rac1·GTP. Crystal structures reveal that activated Rac1 and RhoA use their effector-binding surfaces to associate with the same hydrophobic surface on the PH domain. Both activated RhoA and Rac1 can stimulate exchange of nucleotide on RhoA by localization of p190RhoGEF to its substrate, RhoA·GDP, in vitro. The binding of activated RhoA provides a mechanism for positive feedback regulation as previously proposed for the family of Lbc RhoGEFs. In contrast, the novel interaction between activated Rac1 and p190RhoGEF reveals a potential mechanism for cross-talk regulation where Rac can directly effect stimulation of RhoA. The greater capacity of Rac1 to stimulate p190RhoGEF among the Lbc RhoGEFs suggests functional specialization.