Skip to main content

Kuhn Lab at The Scripps Research Institute.

Go Search
Kuhn Lab at The Scripps Research Institute.
About the Kuhn Lab
About the Stevens Lab
News and Publications
People
Projects & Labs
Getting Involved
Former Members
  
Kuhn Lab at The Scripps Research Institute. > KSPublications > Structural Basis of Guanine Nucleotide Exchange Mediated by the T-cell Essential Vav1  

KSPublications: Structural Basis of Guanine Nucleotide Exchange Mediated by the T-cell Essential Vav1

Title

Structural Basis of Guanine Nucleotide Exchange Mediated by the T-cell Essential Vav1 

Authors

Chrencik, J.E., Brooun, A., Zhang, H., Mathews, I.I., Hura, G.L., Foster, S.A., Perry, J.J.P., Streiff, M., Ramage, P., Widmer, H., Bokoch, G.M., Tainer, J., Weckbecker, G. & Kuhn, P. 

Abstract

The guanine nucleotide exchange factor (GEF) Vav1 plays an important role in T-cell activation and tumorigenesis. In the GEF superfamily, Vav1 has the ability to interact with multiple families of RhoGTPases. The structure of the Vav1-DH-PH-CRD/Rac1 complex to 2.6 Å resolution reveals a unique intramolecular network of contacts between the Vav-1 cysteine rich domain (CRD) and the C-terminal helix of the Vav1 Dbl homology (DH) domain. These unique interactions stabilize the Vav-1 DH domain for its intimate association with the Switch-II region of Rac1 that is critical for the displacement of the guanine nucleotide. Further, a mutational analysis confirms that the atypical CRD is critical for maintaining both optimal guanine nucleotide exchange activity and broader specificity of Vav family GEFs. Taken together, the data outline the detailed nature of Vav1’s ability to contact a range of RhoGTPases using a novel protein-protein interaction network.

Journal

Journal of Molecular Biology 

Year

2008 

Date

5/17/2008 

Link

Article 

Reference

Chrencik, J.E., Brooun, A., Zhang, H., Mathews, I.I., Hura, G.L., Foster, S.A., Perry, J.J.P., Streiff, M., Ramage, P., Widmer, H., Bokoch, G.M., Tainer, J., Weckbecker, G. & Kuhn, P., Structural Basis of Guanine Nucleotide Exchange
Mediated by the T-cell Essential Vav1, Journal of Molecular Biology (2008), doi:
10.1016/j.jmb.2008.05.024

PMID

18589439 

Keyword

PPI 

TSRI Number

 
Attachments
Created at 5/23/2008 3:06 PM  by System Account 
Last modified at 4/18/2012 10:51 AM  by Katya Kadyshevskaya