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Related Experiment Videos

The relationship between sequence and interaction divergence in proteins.

Patrick Aloy1, Hugo Ceulemans, Alexander Stark

  • 1Structural and Computational Biology Programme, EMBL Heidelberg, Meyerhofstrasse 1, 69117, Heidelberg, Germany.

Journal of Molecular Biology
|September 23, 2003
PubMed
Summary
This summary is machine-generated.

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Protein domains with high sequence identity (30-40%+) interact similarly. However, shared folds alone rarely guarantee conserved protein-protein interactions, indicating a sequence similarity "twilight zone".

Area of Science:

  • Structural biology
  • Bioinformatics
  • Protein interaction analysis

Background:

  • A knowledge gap exists between protein complexes with known 3D structures and those identified via methods like affinity purification or the two-hybrid system.
  • Extrapolating interaction data from known structures to homologous proteins is crucial for bridging this gap.
  • Understanding if and how proteins of the same type (family, superfamily, fold) interact is key for accurate extrapolation.

Purpose of the Study:

  • To investigate whether homologous protein domains interact in a conserved manner across different protein complexes.
  • To determine the relationship between sequence similarity, structural fold similarity, and interaction conservation in protein domains.

Main Methods:

  • Identified instances of identical domain pairs interacting in different complexes within the Structural Classification of Proteins (SCOP) database.

Related Experiment Videos

  • Quantified interaction similarity using interaction Root Mean Square Deviation (RMSD).
  • Correlated interaction similarity with protein sequence identity and fold similarity.

    • Main Results:

    • Protein domains with high sequence identity (≥30-40%) consistently exhibit similar interaction modes.
    • Similarity solely based on protein fold, without evidence of common ancestry, rarely correlates with conserved interactions.
    • A 'twilight zone' of sequence similarity exists where predicting interaction conservation is uncertain.

    Conclusions:

    • High sequence identity is a strong predictor of conserved protein-protein interactions.
    • Structural fold similarity alone is insufficient to infer conserved interactions.
    • The findings highlight the importance of sequence information for predicting interaction patterns in structural bioinformatics.