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Regulation of small GTPases by GEFs, GAPs, and GDIs.
TLDR
An overview of the current knowledge of the many facets of small GTPase regulation is presented, including multilayered autoinhibition with stepwise release, feedback loops mediated by the activated GTPases, feed-forward signaling flow between regulators and effectors, and a phosphorylation code for RhoGDIs.
Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy?
TLDR
This Review assesses the association of GEFs and GAPs with cancer and their druggability for cancer therapeutics.
Brefeldin A acts to stabilize an abortive ARF-GDP-Sec7 domain protein complex: involvement of specific residues of the Sec7 domain.
TLDR
It is shown that the target of BFA inhibition of ARF exchange activity is an ARF-GDP-Sec7 domain protein complex, and that BFA acts to stabilize this complex to a greater extent for a BFA-sensitive Sec7 domain than for a resistant one.
Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor
TLDR
The crystal structures of these intermediates show that membrane recruitment of Arf and nucleotide dissociation are separate reactions stimulated by Sec7, and reveal unexplored ways in which to inhibit the activation of small G proteins.
GEFs: structural basis for their activation of small GTP-binding proteins.
TLDR
A deeper understanding of the mechanisms of activation of Ras-like GTP-binding proteins is suggested and how they might represent targets for therapeutic intervention is suggested.
Structure of the Sec7 domain of the Arf exchange factor ARNO
TLDR
The crystal structure of the Sec7 domain of human ARNO at 2 Å resolution is reported and the identification of the site of interaction of ARNO with Arf is identified, indicating the exchange-factor activity was first found in Sec7, a yeast protein involved in secretion.
RhoGDIs Revisited: Novel Roles in Rho Regulation
TLDR
Recent structure‐function relationships and cellular studies on rhoGDIs are surveyed and their classical housekeeping role into novel and more specific functions are revisited and their involvement in diseases is reviewed.
Arf, Arl, Arp and Sar proteins: a family of GTP‐binding proteins with a structural device for ‘front–back’ communication
TLDR
The sequence and structural determinants that propagate information across the protein are defined and it is proposed that Arf family members with the interswitch toggle device are activated by a bipartite mechanism acting on opposite sides of the protein.
Nomenclature for the human Arf family of GTP-binding proteins: ARF, ARL, and SAR proteins
TLDR
This work proposes a more consistent nomenclature for the human members of the Arf family that may also serve as a guide for nomenClature in other species.
Redox signalling in the chloroplast: structure of oxidized pea fructose‐1,6‐bisphosphate phosphatase
TLDR
The structure of the oxidized, low‐activity form of chloroplastic fructose‐1,6‐bisphosphate phosphatase (FBPase), one of the four enzymes of the Calvin cycle whose activity is redox‐regulated by light, is reported, providing a structural basis for redox regulation in the chloroplast.
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