Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Intrinsically Disordered Proteins02:18

Intrinsically Disordered Proteins

18.1K
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...
18.1K
Conserved Binding Sites01:49

Conserved Binding Sites

4.3K
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...
4.3K
Protein Folding01:25

Protein Folding

8.4K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
8.4K
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

11.2K
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...
11.2K
Ligand Binding Sites02:40

Ligand Binding Sites

13.1K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
13.1K
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

18.3K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
18.3K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Detangling knots: the intricate roles of G-quadruplexes in herpesvirus replication.

Journal of virology·2026
Same author

DL3D: visual representation of conformational ensembles of domain-linker-domain proteins.

BMC bioinformatics·2026
Same author

Distinguishing near- versus off-critical phase behaviors of intrinsically disordered proteins.

Reports on progress in physics. Physical Society (Great Britain)·2026
Same author

Short autoinhibitory sequences control phase separation of an essential bacterial transcription termination factor.

The EMBO journal·2026
Same author

Synergistic antiviral effects of structure-guided peptides and a mutagenic base analog on SARS-CoV-2 replication.

Antimicrobial agents and chemotherapy·2026
Same author

LinkCraft: An interactive tool for the design of flexible linkers.

Journal of molecular biology·2026

Related Experiment Video

Updated: Sep 2, 2025

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

7.4K

Conformational buffering underlies functional selection in intrinsically disordered protein regions.

Nicolás S González-Foutel1,2, Juliana Glavina1,3, Wade M Borcherds4

  • 1Instituto de Investigaciones Biotecnológicas (IIBiO-CONICET), Universidad Nacional de San Martín, Buenos Aires, Argentina.

Nature Structural & Molecular Biology
|August 10, 2022
PubMed
Summary

Disordered proteins like adenovirus E1A use conformational buffering to maintain function despite sequence changes. This involves compensatory changes in motifs and linkers, explaining functional selection in these adaptable proteins.

More Related Videos

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

2.0K
Author Spotlight: Unlocking the World of Intrinsically Disordered Regions with Cellular Sensing and Responses
05:13

Author Spotlight: Unlocking the World of Intrinsically Disordered Regions with Cellular Sensing and Responses

Published on: January 12, 2024

1.1K

Related Experiment Videos

Last Updated: Sep 2, 2025

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

7.4K
Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

2.0K
Author Spotlight: Unlocking the World of Intrinsically Disordered Regions with Cellular Sensing and Responses
05:13

Author Spotlight: Unlocking the World of Intrinsically Disordered Regions with Cellular Sensing and Responses

Published on: January 12, 2024

1.1K

Area of Science:

  • Molecular biology
  • Biochemistry
  • Genetics

Background:

  • Disordered proteins often maintain function despite sequence variation.
  • Identifying mechanisms of functional selection in these proteins is challenging.
  • Adenovirus early gene 1A (E1A) protein is a key regulator of cell cycle.

Purpose of the Study:

  • To elucidate the molecular mechanism of functional selection for the disordered E1A protein.
  • To understand how E1A achieves high-affinity binding to the retinoblastoma (Rb) protein.
  • To investigate the role of disordered linkers in protein function and evolution.

Main Methods:

  • Analysis of E1A protein structure-function relationships.
  • Investigating binding interactions between E1A, Rb protein, and host factors.
  • Studying sequence variation and coevolution in E1A protein families.

Main Results:

  • E1A utilizes two binding motifs tethered by a disordered linker for picomolar affinity Rb binding.
  • Compensatory sequence changes in motifs and linkers maintain optimal tethering (conformational buffering).
  • Coevolution of motifs and linker preserves or alters the E1A tethering mechanism.

Conclusions:

  • Conformational buffering and motif-linker coevolution explain functional robustness in disordered E1A linkers.
  • These mechanisms contribute to functional selection in hypervariable disordered protein regions.
  • The findings provide insights into the evolution and adaptation of disordered proteins.