Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Protein-Protein Interfaces

Protein-Protein Interfaces

Protein-protein Interfaces

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...

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...

Conserved Binding Sites

Conserved Binding Sites

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...

Protein Networks

Protein Networks

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...

You might also read

Related Articles

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

Sort by

Same author

High-resolution structure of monomorphic Aβ<sub>1-40</sub> fibrils.

Proceedings of the National Academy of Sciences of the United States of America·2026

Same author

Effects of single synonymous substitutions on fold efficiency demonstrate the influence of rare codons and protein structure.

Cell reports·2026

Same author

Accurate prediction of substitution rates at protein sites with a mutation-selection model.

Scientific reports·2025

Same author

Effects of solution conditions on the self-assembly of the chaperone protein DNAJB6b.

Communications chemistry·2025

Same author

Comparative Study of Three Diverse Glycogen Branching Enzymes for Efficient Generation of Highly Surface Branched Starch Granules with Enhanced Digestive Resistance.

Journal of agricultural and food chemistry·2025

Same author

Applying the Sabatier Principle to Decipher the Surface-Structure-Dependent Catalysis of Different Starch Granules by Pullulanase.

JACS Au·2025

Search research articles

Related Experiment Video

Updated: Nov 9, 2025

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

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

Published on: July 14, 2015

An ultra-high affinity protein-protein interface displaying sequence-robustness.

Marie Sofie Møller^1,2, Sita Vaag Olesen², Ingemar André¹

¹Biochemistry and Structural Biology, Lund University, Lund, Sweden.

Protein Science : a Publication of the Protein Society

|April 10, 2021

Summary

Ultra-high affinity protein interactions can tolerate mutations at the interface without losing binding strength. This suggests protein complexes are robust to evolutionary changes, even without traditional hotspot residues.

Keywords:

computational protein redesign non-hotspot-centric interactions protein-protein complex proteinaceous inhibitor surface plasmon resonance

More Related Videos

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

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

Published on: January 26, 2024

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Published on: July 8, 2025

Related Experiment Videos

Last Updated: Nov 9, 2025

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

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

Published on: July 14, 2015

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

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

Published on: January 26, 2024

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Published on: July 8, 2025

Area of Science:

Biochemistry
Structural Biology
Protein Engineering

Background:

Protein-protein interactions are vital in biological systems, including immune responses, signaling, and enzyme regulation.
Ultra-high affinity interactions (K_d <0.1 nM) are observed but their structural and energetic basis remains unclear.
The barley limit dextrinase (LD) and its inhibitor (LDI) form an ultra-high affinity complex (K_d = 42 pM).

Purpose of the Study:

To investigate the robustness of the ultra-high affinity LD-LDI complex to sequence variations at the protein-protein interface.
To determine if alternative LDI sequences can maintain ultra-high binding affinity.
To understand the energetic contributions to ultra-high affinity interactions.

Main Methods:

Computational protein redesign was employed to engineer LDI variants.
Variants with diverse mutations beyond conservative substitutions were created.
Surface plasmon resonance (SPR) was used to analyze binding affinities of LDI variants to LD.

Main Results:

High affinity of the LD-LDI complex depends on rim interactions, not central hotspot residues.
LDI variants with substitutions, including those with different functional groups, retained ultra-high affinity.
Energetic coupling between distant interface residues was observed.

Conclusions:

Ultra-high binding affinity can be achieved without hotspot residues, enhancing complex stability against mutations.
The LD-LDI interface demonstrates a non-classical arrangement contributing to robust binding.
This finding has implications for understanding protein complex evolution and engineering stable protein interactions.