PDBsum entry 2oj4

Signaling protein inhibitor

PDB id: 2oj4

Contents

Protein chain

127 a.a. *

Waters ×62

* Residue conservation analysis

PDB id:

2oj4

Name:

Signaling protein inhibitor

Title:

Crystal structure of rgs3 rgs domain

Structure:

Regulator of g-protein signaling 3. Chain: a. Fragment: rgs domain. Synonym: rgs3. Rgp3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rgs3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.30Å R-factor: 0.221 R-free: 0.250

Authors:

E.Boura,T.Obsil

Key ref:

L.Rezabkova et al. (2010). 14-3-3 protein interacts with and affects the structure of RGS domain of regulator of G protein signaling 3 (RGS3). J Struct Biol, 170, 451-461. PubMed id: 20347994

Date:

12-Jan-07 Release date: 30-Jan-07

Protein chain

P49796  (RGS3_HUMAN) -  Regulator of G-protein signaling 3 from Homo sapiens

Seq: 1198 a.a.

Struc: 127 a.a.

J Struct Biol 170:451-461 (2010)

PubMed id: 20347994

14-3-3 protein interacts with and affects the structure of RGS domain of regulator of G protein signaling 3 (RGS3).

L.Rezabkova, E.Boura, P.Herman, J.Vecer, L.Bourova, M.Sulc, P.Svoboda, V.Obsilova, T.Obsil.

ABSTRACT

Regulator of G protein signaling (RGS) proteins function as GTPase-activating proteins (GAPs) for the alpha-subunit of heterotrimeric G proteins. Several RGS proteins have been found to interact with 14-3-3 proteins. The 14-3-3 protein binding inhibits the GAP function of RGS proteins presumably by blocking their interaction with G(alpha) subunit. Since RGS proteins interact with G(alpha) subunits through their RGS domains, it is reasonable to assume that the 14-3-3 protein can either sterically occlude the G(alpha) interaction surface of RGS domain and/or change its structure. In this work, we investigated whether the 14-3-3 protein binding affects the structure of RGS3 using the time-resolved tryptophan fluorescence spectroscopy. Two single-tryptophan mutants of RGS3 were used to study conformational changes of RGS3 molecule. Our measurements revealed that the 14-3-3 protein binding induces structural changes in both the N-terminal part and the C-terminal RGS domain of phosphorylated RGS3 molecule. Experiments with the isolated RGS domain of RGS3 suggest that this domain alone can, to some extent, interact with the 14-3-3 protein in a phosphorylation-independent manner. In addition, a crystal structure of the RGS domain of RGS3 was solved at 2.3A resolution. The data obtained from the resolution of the structure of the RGS domain suggest that the 14-3-3 protein-induced conformational change affects the region within the G(alpha)-interacting portion of the RGS domain. This can explain the inhibitory effect of the 14-3-3 protein on GAP activity of RGS3.