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Related Experiment Videos

Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm.

P E Wright1, H J Dyson

  • 1Department of Molecular Biology and Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. wright@scrips.edu

Journal of Molecular Biology
|November 5, 1999
PubMed
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Many proteins lack a fixed structure, challenging function prediction. These intrinsically disordered proteins play key regulatory roles, offering functional advantages and enabling cellular control.

Area of Science:

  • Structural Biology
  • Proteomics
  • Genomics

Background:

  • Determining protein functions is a major post-genome challenge.
  • A significant portion of sequenced genes code for non-globular or unfolded protein sequences.
  • The function of proteins is often assumed to be directly linked to their three-dimensional structure.

Purpose of the Study:

  • To investigate the conformational propensities and functions of non-globular protein sequences.
  • To re-examine the assumption that a folded three-dimensional structure is necessary for protein function.
  • To understand the role of intrinsically disordered proteins in cellular regulation.

Main Methods:

  • Bioinformatic analysis of genomic sequences to identify non-globular protein regions.

Related Experiment Videos

  • Experimental characterization of protein conformational states in solution and upon target binding (implied).
  • Literature review of known examples of intrinsically disordered proteins in regulatory pathways.
  • Main Results:

    • A high proportion of non-globular sequences exist across all studied genomes, suggesting important evolutionary roles.
    • Numerous proteins function effectively without a stable, intrinsic globular structure.
    • Lack of intrinsic structure can confer advantages, such as multi-target binding and regulated binding thermodynamics.

    Conclusions:

    • Intrinsically disordered proteins are crucial for cellular regulation, including cell cycle control and gene regulation.
    • Disordered regions often adopt structure upon binding to their targets.
    • The dynamic nature of these proteins facilitates rapid cellular responses and controlled turnover.