The Dock Family of Atypical Guanine Nucleotide Exchange Factors: Regulation by ELMO1 and RhoG Public Deposited
- Last Modified
- March 20, 2019
- Creator
-
Holley, Cynthia
- Affiliation: School of Medicine, Department of Biochemistry and Biophysics
- Abstract
- The Dock family of proteins regulates diverse biological processes including cell migration, phagocytosis and neuronal polarization. These proteins contain a unique type of guanine nucleotide exchange factor (GEF) domain, and function as GEFs for Rho-family GTPases. Several Dock-family proteins form complexes with ELMO proteins and the Dock/ELMO complex acts as a bi-partite GEF for Rac. Molecular details of how the Dock/ELMO complexes bind and exchange nucleotide on Rac are critical for our understanding of their biological effects, yet remain poorly defined. As described here, purified Dock2/ELMO1 complex is a stable heterotetramer composed of two molecules each of Dock2 and ELMO1. This heterotetramer coordinates a single molecule of nucleotide-free Rac. We identify an inhibitory conformation within ELMO1 mediated through contacts between the N- and C-terminal regions of ELMO1 and describe a mechanism for relief of this inhibition through the binding of RhoG, another Rho-family GTPase. The interaction between RhoG and ELMO1 is both nucleotide-dependent, and dependent upon the C-terminal polybasic region of RhoG. These data provide fundamentally important molecular insights into the composition of the Dock/ELMO complex and regulation of nucleotide exchange via the Dock/ELMO proteins.
- Date of publication
- May 2008
- Keyword
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Dohlman, Henrik
- Kuhlman, Brian
- Redinbo, Matthew R.
- Hall, Traci
- Sondek, John
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2008
- Language
- Access
- This item is restricted from public view for 1 year after publication.
- Parents:
This work has no parents.
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