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Invited review: Small GTPases and their GAPs
Ashwini K Mishra1, David G Lambright1
1Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605.
Biopolymers
|March 15, 2016
Summary
Small GTPases regulate biological processes through a conformational switch. Guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) control this cycle, with GAPs accelerating GTP hydrolysis.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Small GTPases are crucial regulatory hubs in diverse biological systems.
- They cycle between active (GTP-bound) and inactive (GDP-bound) states via a conformational switch.
- Guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) modulate this cycle.
Purpose of the Study:
- To review current understanding of intrinsic and GAP-catalyzed GTP hydrolysis in small GTPases.
- To explore structural, molecular, and chemical mechanistic perspectives.
- To highlight the diversity in reaction mechanisms and catalytic acceleration by GAPs.
Main Methods:
- Review of existing literature.
- Analysis of structural, molecular, and chemical mechanistic data.
- Integration of experimental and in silico approaches.
Main Results:
- The GTPase cycle, while seemingly simple, involves complex and diverse structural bases for GTP hydrolysis.
- Catalytic acceleration by GAPs exhibits significant structural and mechanistic variability.
- A consensus view is emerging for well-studied small GTPase paradigms.
Conclusions:
- Despite progress, fundamental aspects of small GTPase reaction mechanisms remain challenging to fully elucidate.
- Recent findings suggest ongoing discoveries and a need for further research.
- Understanding these mechanisms is key to comprehending cellular regulation.
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