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Related Concept Videos

Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Mechanical Protein Functions01:58

Mechanical Protein Functions

Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force. 
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Tension Response at Adherens Junctions01:26

Tension Response at Adherens Junctions

The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...

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Related Experiment Videos

Large amplitude conformational change in proteins explored with a plastic network model: adenylate kinase.

Paul Maragakis1, Martin Karplus

  • 1Department of Chemistry and Chemical Biology, Harvard University, Cambridge MA 02138, USA. maragakis@cmt.harvard.edu

Journal of Molecular Biology
|September 6, 2005
PubMed
Summary

The plastic network model reveals conformational changes in Escherichia coli adenylate kinase by connecting open and closed structures. This analysis identifies key protein hinges involved in the transition, validated by existing structural data.

Related Experiment Videos

Area of Science:

  • Structural Biology
  • Biophysics
  • Computational Biology

Background:

  • Proteins undergo conformational changes essential for their function.
  • Understanding these transitions is crucial for drug design and protein engineering.
  • Escherichia coli adenylate kinase serves as a model system for studying protein dynamics.

Purpose of the Study:

  • To generate a conformational change pathway for Escherichia coli adenylate kinase.
  • To identify and analyze the minimal energy pathways between open and closed conformers.
  • To validate the identified protein hinges using existing structural data.

Main Methods:

  • Application of the plastic network model (PNM) to connect energy basins of known conformers.
  • Analysis of minimal energy pathways between identified energy basins.
  • Evaluation of elastic energy distribution and C(alpha) pseudo-dihedral variations.
  • Comparison of the generated pathway with an ensemble of 45 published protein structures.

Main Results:

  • The plastic network model successfully generated a conformational change pathway for adenylate kinase.
  • Key protein hinges involved in the open-to-closed transition were identified and agreed with existing definitions.
  • The elastic energy distribution and C(alpha) pseudo-dihedral variations corroborated the hinge identification.
  • The generated pathway remained within 3.0 Å of 45 published structures, indicating high fidelity.

Conclusions:

  • The plastic network model is effective for elucidating protein conformational pathways.
  • The identified hinges are critical for the functional conformational change of adenylate kinase.
  • The model provides a robust framework for analyzing protein dynamics and structural transitions.