The Dock Family of Atypical Guanine Nucleotide Exchange Factors: Regulation by ELMO1 and RhoG Public Deposited

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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.
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  • In Copyright
Advisor
  • Dohlman, Henrik
  • Kuhlman, Brian
  • Hall, Traci
  • Sondek, John
  • Redinbo, Matthew R.
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2008
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