Related Experiment Video
Updated: Aug 8, 2026
11:28
Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates
Published on: March 31, 2012
The many faces of Ras: recognition of small GTP-binding proteins
1Dept of Molecular and Cellular Biology, 229 Stanley Hall #3206, University of California, Berkeley, CA 94720-3206, USA. korbett@uclink4.berkeley.edu
Trends in Biochemical Sciences
|December 12, 2001
Summary
Small GTP-binding proteins interact with partners in diverse ways, not a single site. A new interface array method reveals at least nine distinct recognition patterns, aiding evolutionary and functional studies.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Over 30 structures of Ras superfamily small GTP-binding proteins complexed with partners are known.
- Previous analyses indicated broad surface accessibility for protein interactions.
Purpose of the Study:
- To introduce a novel analysis technique, the interface array, for quantifying protein-protein contact patterns.
- To characterize the diversity and classification of interaction modes for Ras superfamily proteins.
Main Methods:
- Comparative analysis of known protein complex structures.
- Development and application of the interface array technique to map surface contacts.
- Classification of small GTP-binding protein recognition patterns.
Main Results:
- Ras superfamily proteins exhibit extensive surface contacts, with nearly all positions interacting with at least one partner.
- The interface array method identified at least nine distinct classes of small GTP-binding protein recognition.
- Proteins with similar functions, even those with different folds, utilize similar interaction strategies.
Conclusions:
- Small GTP-binding protein interactions are highly diverse, defying a single consensus binding site model.
- The identified classes of shared surface contacts suggest convergent and divergent evolution in protein-protein interactions.
- Specific effector functions are likely dictated by particular protein-protein contact configurations.
Related Concept Videos
02:14GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
01:14Rab Proteins
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
02:14GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...