Related Experiment Video
Updated: Aug 6, 2026
10:37
Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
Sequence and 3D structural relationships between mammalian Ras- and Rho-specific GTPase-activating proteins (GAPs):
T P Calmels1, I Callebaut, I Léger
1Smithkline-Beecham Laboratoires Pharmaceutiques, Saint-Grégoire, France.
FEBS Letters
|May 23, 1998
Summary
Ras- and Rho-specific GTPase-activating proteins (GAPs) share a hidden 3D structural scaffold, indicating a close evolutionary relationship. This discovery, centered on the
Area of Science:
- Biochemistry and structural biology
- Molecular and cellular biology
- Protein structure and function
Background:
- Ras- and Rho-specific GTPase-activating proteins (GAPs) are crucial regulators of small GTPase signaling.
- Previous studies have not identified a structural relationship between these two GAP subfamilies.
- Both subfamilies share similar domain sizes and target structurally related proteins (Ras and Rho).
Purpose of the Study:
- To investigate the potential structural relationship between Ras- and Rho-specific GAPs.
- To identify conserved structural features and evolutionary links between these GAP subfamilies.
Main Methods:
- Utilized hydrophobic cluster analysis (HCA) to compare sequence similarities with 3D structural data.
- Analyzed 3D structures of p120rasGAP and p50rhoGAP.
- Extended analysis to other members of both subfamilies.
Main Results:
- Identified shared 3D scaffolds between Ras- and Rho-specific GAPs, revealing a previously undetected relationship.
- Confirmed conserved geometry of key residues (e.g., arginines and stabilizing residues) across subfamilies.
- Defined an invariant motif of three consecutive helices, termed the 'cradle fold', as the core structural element.
Conclusions:
- Ras- and Rho-specific GAPs share a common evolutionary origin and structural framework.
- The 'cradle fold' motif is central to the conserved structure and function of these GAPs.
- This finding provides new insights into the specific regulation mechanisms of small GTPases.
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