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Protein Interaction and Genetic Disease

  1. Niels Gregersen1,
  2. Peter Bross1,
  3. Rikke KJ Olsen1,
  4. Johan Palmfeldt1,
  5. Thomas J Corydon2

Published Online: 15 FEB 2011

DOI: 10.1002/9780470015902.a0021450



How to Cite

Gregersen, N., Bross, P., Olsen, R. K., Palmfeldt, J. and Corydon, T. J. 2011. Protein Interaction and Genetic Disease. eLS. .

Author Information

  1. 1

    Aarhus University Hospital, Skejby, Aarhus, Denmark

  2. 2

    Aarhus University, Institute of Human Genetics, Aarhus, Denmark

Publication History

  1. Published Online: 15 FEB 2011


The function of proteins is dependent on other proteins. Proteins function as oligomers, complexes, super-complexes or higher order networks, in which they interact with each other, either temporarily when they exert their function or ‘permanently’ in functional units. Genetic defects in single proteins may therefore, in addition to disturbing the specific function of the defective protein, disturb other functions that are dependent on it. In this review we will discuss how the two main types of defects in genetic disease, truncating variations (stop-codon introductions and small out-of-frame deletions/insertions) and in-frame variations (missense variations and small in-frame deletions/insertions), may disturb normal interactions. Depending on the importance (location) of the missing or aberrant protein, the effect on the cellular pathway or interacting network may be severe or mild. Protein interactions and disturbances therein may be determined by protein mass spectrometry after immuno-precipitation or other fractionation and separation methods.

Key Concepts:

  • Cellular proteins interact in oligomer and complex structures as well as in higher order networks.

  • Protein interactions may be permanent in the lifetime of proteins or temporary during their function.

  • Genetic defects may disturb interactions between proteins depending on the nature of the defect and type of interaction.

  • Missing proteins due to truncation, comprising big deletions, small out-of-frame deletions/insertions and severe splice alteration, may abolish the function of oligomers, complexes, pathways and networks.

  • Aberrant proteins due to missense variations and in-frame deletions/insertions may disturb interactions with protein partners in oligomers, complexes and networks.

  • Missing and aberrant proteins in branch-points (nodes) have as a role severe consequences, resulting in genotype–phenotype association.

  • Missing and aberrant proteins in redundant pathways have variable consequences, resulting in poor genotype–phenotype association.

  • Missing and aberrant proteins in molecular machines, such as the chaperonin Hsp60, may elicit pleotropic effects due to defective processing of client proteins.

  • Protein interactions and disturbances therein may be determined experimentally by protein mass spectrometry (MS), preceded by immunoprecipitation of target proteins, either directly or after cross-linking, or indicated after mild solubilisation followed by extensive separating procedures and MS.

  • The challenge is to design experiments that can determine qualitative and quantitative disturbances of proteins interactions in cells and tissue from patients, model animals and model cells compared to interactions in normal cells and tissue.


  • aberrant protein structures;
  • disturbed protein interaction;
  • protein complexes;
  • protein super-complexes;
  • protein networks;
  • protein quality control;
  • metabolon structures;
  • metabolic channelling;
  • determination of protein interaction;
  • structural mass spectrometry