PH domain of ELMO functions in trans to regulate Rac activation via Dock180

@article{Lu2004PHDO,
  title={PH domain of ELMO functions in trans to regulate Rac activation via Dock180},
  author={Mingjian Lu and Jason Michael Kinchen and Kent L. Rossman and Cynthia M. Grimsley and C Debakker and Enrico Brugnera and Annie-Carole Tosello-Trampont and Lisa B. Haney and Doris Klingele and John Sondek and Michael O. Hengartner and Kodi S. Ravichandran},
  journal={Nature Structural \&Molecular Biology},
  year={2004},
  volume={11},
  pages={756-762}
}
The members of the Dock180 superfamily of proteins are novel guanine nucleotide exchange factors (GEF) for Rho family GTPases and are linked to multiple biological processes from worms to mammals. ELMO is a critical regulator of Dock180, and the Dock180–ELMO complex functions as a bipartite GEF for Rac. We identified a mechanism wherein the PH domain of ELMO, by binding the Dock180–Rac complex in trans, stabilizes Rac in the nucleotide-free transition state. Mutagenesis studies reveal that this… 
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TLDR
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TLDR
The authors provide mechanistic insights into how ELMO1 regulates DOCK2 activity by determining the structure of the Docks2–ELMO1 binary complex representing the closed, auto-inhibited state and the Dock2−EL MO1−RAC1 ternary complex structure, where DOCK 2−ELMO 1 adopts an open, active conformation.
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References

SHOWING 1-10 OF 36 REFERENCES
Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex
TLDR
A domain within Dock180 is identified that specifically recognizes nucleotide-free Rac and can mediate GTP loading of Rac in vitro and it is proposed that the Dock180–ELMO complex functions as an unconventional two-part exchange factor for Rac.
Dock180 and ELMO1 Proteins Cooperate to Promote Evolutionarily Conserved Rac-dependent Cell Migration*
TLDR
This finding suggests that Rac activation by the ELMO·Dock180 complex at discrete intracellular locations mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration.
RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo
TLDR
It is shown that RhoG activates Rac1 through Elmo and Dock180 to control cell morphology and interacts directly with Elmo in a GTP-dependent manner and forms a ternary complex with Dock 180 to induce activation of Rac1.
Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1
TLDR
The Tiam1/Rac1 structure highlights the interactions that catalyse nucleotide exchange on RhoFamily G proteins, and illustrates structural determinants dictating specificity between individual Rho family members and their associated Dbl-related guanine nucleotide Exchange factors.
A crystallographic view of interactions between Dbs and Cdc42: PH domain‐assisted guanine nucleotide exchange
TLDR
Comparative sequence analysis suggests that a subset of Dbl‐family proteins will utilize their PH domains similarly to Dbs, and the Dbs PH domain participates with the DH domain in binding Cdc42, primarily through a set of interactions involving switch 2 of the GTPase.
Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins
TLDR
Sequence comparison combined with mutational analysis suggest that CZH2 is a new GEF domain for the Rho family of proteins, a new superfamily that includes the so-called 'CDM' proteins that bind to and activate Rac.
Quantitative Analysis of the Effect of Phosphoinositide Interactions on the Function of Dbl Family Proteins*
TLDR
It is demonstrated that the conserved PH domains of three distinct Dbl family proteins, intersectin, Dbs, and Tiam1, selectively bind lipid vesicles only when phosphoinositides are present, suggesting that unless all relevant components are localized to a lipid membrane surface, D Bl family GEFs generally are not intrinsically modulated by binding phosphoinposides.
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