Recognition of the Activated States of Gα13 by the rgRGS Domain of PDZRhoGEF

Zhe Chen, William D. Singer, Shahab M. Danesh, Paul C. Sternweis, Stephen R. Sprang

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

G12 class heterotrimeric G proteins stimulate RhoA activation by RGS-RhoGEFs. However, p115RhoGEF is a GTPase Activating Protein (GAP) toward Gα13, whereas PDZRhoGEF is not. We have characterized the interaction between the PDZRhoGEF rgRGS domain (PRG-rgRGS) and the alpha subunit of G13 and have determined crystal structures of their complexes in both the inactive state bound to GDP and the active states bound to GDP•AlF (transition state) and GTPγS (Michaelis complex). PRG-rgRGS interacts extensively with the helical domain and the effector-binding sites on Gα13 through contacts that are largely conserved in all three nucleotide-bound states, although PRG-rgRGS has highest affinity to the Michaelis complex. An acidic motif in the N terminus of PRG-rgRGS occupies the GAP binding site of Gα13 and is flexible in the GDP•AlF complex but well ordered in the GTPγS complex. Replacement of key residues in this motif with their counterparts in p115RhoGEF confers GAP activity.

Original languageEnglish (US)
Pages (from-to)1532-1543
Number of pages12
JournalStructure
Volume16
Issue number10
DOIs
StatePublished - Oct 8 2008

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Rho Guanine Nucleotide Exchange Factors
GTPase-Activating Proteins
Binding Sites
Heterotrimeric GTP-Binding Proteins
Protein Binding
Nucleotides

Keywords

  • MICROBIO
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Recognition of the Activated States of Gα13 by the rgRGS Domain of PDZRhoGEF. / Chen, Zhe; Singer, William D.; Danesh, Shahab M.; Sternweis, Paul C.; Sprang, Stephen R.

In: Structure, Vol. 16, No. 10, 08.10.2008, p. 1532-1543.

Research output: Contribution to journalArticle

Chen, Zhe ; Singer, William D. ; Danesh, Shahab M. ; Sternweis, Paul C. ; Sprang, Stephen R. / Recognition of the Activated States of Gα13 by the rgRGS Domain of PDZRhoGEF. In: Structure. 2008 ; Vol. 16, No. 10. pp. 1532-1543.
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AU - Sprang, Stephen R.

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