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Conservation of Protein Domains Over Different Proteins

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...

Conservation of Protein Domains

Conservation of Protein Domains

Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...

Protein Organization

Protein Organization

Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.

Conserved Binding Sites

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...

Protein Folding

Protein Folding

Intrinsically Disordered Proteins

Intrinsically Disordered Proteins

Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...

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Related Experiment Video

Updated: Jun 12, 2026

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

Published on: July 16, 2017

Automated electron-density sampling reveals widespread conformational polymorphism in proteins.

P Therese Lang¹, Ho-Leung Ng, James S Fraser

¹Department of Molecular and Cell Biology, University of California, Berkeley, California 97420-3220, USA.

Protein Science : a Publication of the Protein Society

|May 26, 2010

Summary

Proteins exist in multiple shapes, but X-ray crystallography often shows only one. A new tool, Ringer, reveals hidden protein conformations in existing data, showing proteins are more dynamic than previously thought.

More Related Videos

Fully Autonomous Characterization and Data Collection from Crystals of Biological Macromolecules

Fully Autonomous Characterization and Data Collection from Crystals of Biological Macromolecules

Published on: March 22, 2019

Related Experiment Videos

Last Updated: Jun 12, 2026

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

Published on: July 16, 2017

Fully Autonomous Characterization and Data Collection from Crystals of Biological Macromolecules

Fully Autonomous Characterization and Data Collection from Crystals of Biological Macromolecules

Published on: March 22, 2019

Area of Science:

Structural Biology
Biophysics
Computational Biology

Background:

Proteins exist as dynamic ensembles of multiple conformations.
Traditional X-ray crystallography models often represent proteins using a single conformation.
This simplification may obscure functionally relevant protein dynamics.

Purpose of the Study:

To develop a computational method to systematically detect low-population protein conformations from X-ray diffraction data.
To investigate the prevalence of hidden conformational states in existing protein structures.
To explore the relationship between alternate conformations and protein function, such as ligand recognition.

Main Methods:

Development of the Ringer program for systematic sampling of protein side-chain dihedral angles.
Analysis of electron density maps to identify weak, nonrandom features indicative of alternate conformations.
Statistical validation of identified features against traditional noise thresholds.
Application of Ringer to a diverse set of 402 protein structures and high-resolution calmodulin datasets.

Main Results:

Ringer identified statistically significant evidence for hidden, low-population conformations in over 18% of modeled residues across diverse structures.
These alternate conformations were detected even at electron density levels typically disregarded as noise.
Analysis of calmodulin revealed shifts in conformational ensembles upon ligand binding, linking alternate states to function.
The study demonstrates that high-resolution electron density maps contain signals below the conventional 1 sigma cutoff.

Conclusions:

Crystalline proteins exhibit greater conformational heterogeneity than currently represented by crystallographic models.
The Ringer program offers an objective method to uncover previously undetected protein conformations.
Identifying these alternate states is crucial for understanding protein folding, dynamics, and function, including ligand interactions.