Related Experiment Video
Updated: May 16, 2026
10:37
Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
Nucleotide binding affects intrinsic dynamics and structural communication in Ras GTPases.
Francesca Fanelli1, Francesco Raimondi
1Department of Life Sciences, via Campi 183, 41125 Modena, Italy. fanelli@unimo.it
Current Pharmaceutical Design
|November 23, 2012
Summary
Ras GTPases are crucial molecular switches in cells. Computational analyses reveal how subtle nucleotide differences dictate their dynamic behavior and communication, supporting an "extended conformational selection model" for their function.
Area of Science:
- Molecular Biology
- Biochemistry
- Structural Biology
Background:
- Ras superfamily proteins are vital guanine nucleotide-binding proteins (G proteins) for intracellular signal transduction.
- These proteins function as molecular switches, cycling between OFF and ON states to regulate cell biology.
Purpose of the Study:
- To provide a comprehensive structural and dynamic view of Ras GTPase functioning mechanisms.
- To infer evolutionary flexibility, intrinsic dynamics, and structural communication features across Ras GTPase families.
Main Methods:
- Extensive computational analyses and comparative analyses of Ras GTPases.
- Examination of structural and dynamic features in different functional states.
Main Results:
- Ras GTPases share a common Ras-like domain topology and nucleotide-binding site despite low sequence similarity.
- Differences in GDP/GTP binding modes, particularly around the GTP γ-phosphate, significantly impact protein dynamics and communication.
- Nucleotide binding actively dictates functional dynamics, structural networks, and communication pathways in Ras GTPases.
Conclusions:
- Subtle local nucleotide interactions lead to significant functional and dynamic differences in Ras GTPases.
- An "extended conformational selection model" likely better describes nucleotide behavior in these molecular switches.
More Related Videos
13:51Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
Published on: November 11, 2018
10:27Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
Related Concept Videos
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:
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...
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...
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...
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...
01:42Directionality of Nuclear Transport
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...