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Cited by 2,272Protein Structure and DynamicsHeat shock proteins researchEnzyme Structure and Function

The DOI matches its Crossref record; 272 of the 272 references it cites were found in a registry or an index.

Intrinsically disordered protein

Dunker, A.Keith, Lawson, J.David, Brown, Celeste J, Williams, Ryan M, Romero, Pedro, Oh, Jeong S, Oldfield, Christopher J, Campen, Andrew M, Ratliff, Catherine M, Hipps, Kerry W, Ausio, Juan, Nissen, Mark S, Reeves, Raymond, Kang, ChulHee, Kissinger, Charles R, Bailey, Robert W, Griswold, Michael D, Chiu, Wah, Garner, Ethan C, Obradovic, Zoran·2001·Journal of Molecular Graphics and Modelling
DOI 10.1016/s1093-3263(00)00138-8
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Abstract

Proteins can exist in a trinity of structures: the ordered state, the molten globule, and the random coil. The five following examples suggest that native protein structure can correspond to any of the three states (not just the ordered state) and that protein function can arise from any of the three states and their transitions. (1) In a process that likely mimics infection, fd phage converts from the ordered into the disordered molten globular state. (2) Nucleosome hyperacetylation is crucial to DNA replication and transcription; this chemical modification greatly increases the net negative charge of the nucleosome core particle. We propose that the increased charge imbalance promotes its conversion to a much less rigid form. (3) Clusterin contains an ordered domain and also a native molten globular region. The molten globular domain likely functions as a proteinaceous detergent for cell remodeling and removal of apoptotic debris. (4) In a critical signaling event, a helix in calcineurin becomes bound and surrounded by calmodulin, thereby turning on calcineurin's serine/threonine phosphatase activity. Locating the calcineurin helix within a region of disorder is essential for enabling calmodulin to surround its target upon binding. (5) Calsequestrin regulates calcium levels in the sarcoplasmic reticulum by binding approximately 50 ions/molecule. Disordered polyanion tails at the carboxy terminus bind many of these calcium ions, perhaps without adopting a unique structure. In addition to these examples, we will discuss 16 more proteins with native disorder. These disordered regions include molecular recognition domains, protein folding inhibitors, flexible linkers, entropic springs, entropic clocks, and entropic bristles. Motivated by such examples of intrinsic disorder, we are studying the relationships between amino acid sequence and order/disorder, and from this information we are predicting intrinsic order/disorder from amino acid sequence. The sequence-structure relationships indicate that disorder is an encoded property, and the predictions strongly suggest that proteins in nature are much richer in intrinsic disorder than are those in the Protein Data Bank. Recent predictions on 29 genomes indicate that proteins from eucaryotes apparently have more intrinsic disorder than those from either bacteria or archaea, with typically > 30% of eucaryotic proteins having disordered regions of length > or = 50 consecutive residues.

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Crossref · 10.1016/s1093-3263(00)00138-8

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Citations

Cites

Research works printed but not linked: 14

  1. Kendrew, 1960, Structure of myoglobin, Nature, 206, 757
  2. Schulz, G.E., Nucleotide Binding Proteins. In: Molecular Mechanism of Biological Recognition, Balaban, M., Ed. Elsevier/North-Holland Biomedical Press, New York, 1979, pp. 79–94
  3. Dunker, 1997, On the importance of being disordered, PDB Newsletter, 81, 3
  4. Bychkova, 1993, The molten globule in vitro and in vivo, Chemtracts - Biochem. Mol. Biol., 4, 133
  5. Sertoli, 1865, e lesistenza di particulari cellule remificate nei canalicoli seminiferi dell’testicolo umano, Morgangni, 7, 31
  6. Romero, 1997, Identifying disordered regions in proteins from amino acid sequences, Proc. I.E.E.E. International Conference on Neural Networks, 1, 90
  7. Dunker, 1998, Protein disorder and the evolution of molecular recognition, Pacific Symp. Biocomputing, 3, 473
  8. Thomas, 1995, The mechanism of force generation in myosin, Biophys. J., 68, 135S
  9. Linderstrom-Lang, 1952, Structure and enzymatic break-down of proteins, Lane Medical Lectures, 6, 117
  10. Linderstrom-Lang, K.U., and Schellman, J.A., Protein structure and enzyme activity. In: The Enzymes, Boyer, P.D., Lardy, H., and Myrback, K., Eds. Academic Press, New York, 1959, pp. 443–510
  11. Williams, 2001, The protein non-folding problem, Pacific Symp. Biocomp., 6, 89
  12. Garner, 1998, Predicting disordered regions from amino acid sequence, Genome Informatics, 9, 201
  13. Chan, 1999, Caspase and calpain substrates, J. Neurosci. Res., 58, 167, 10.1002/(SICI)1097-4547(19991001)58:1<167::AID-JNR16>3.0.CO;2-K · DOI
  14. Bailey, 2000, Clusterin binds through the action of natively disordered regions, Biophysical Journal, 78, 152A

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Metadata

Authors
Dunker, A. K., Lawson, J. D., Brown, C. J., Williams, R. M., Romero, P., Oh, J. S., Oldfield, C. J., Campen, A. M., Ratliff, C. M., Hipps, K. W., Ausio, J., Nissen, M. S., Reeves, R., Kang, C., Kissinger, C. R., Bailey, R. W., Griswold, M. D., Chiu, W., Garner, E. C., & Obradovic, Z.
Affiliations
  • Washington State University (US)
  • Pfizer (United States) (US)
  • Baylor College of Medicine (US)
Corresponding author
Dunker, A.Keith
ORCID
Venue
Journal of Molecular Graphics and Modelling
Publisher
Elsevier BV
Published
2001-02
Volume
19
Issue
1
Pages
26-59
ISSN
1093-3263 (ISSN-L)
DOI
10.1016/s1093-3263(00)00138-8
OpenAlex
W4210968583
Cited by
2,272
References
272
Citations by year
2026: 67 · 2025: 88 · 2024: 89 · 2023: 83 · 2022: 116 · 2021: 119 · 2020: 129 · 2019: 108 · 2018: 123 · 2017: 97 · 2016: 127 · 2015: 111 · 2014: 103 · 2013: 122 · 2012: 113
FWCI
3.13
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
Journal of Molecular Graphics and Modelling (publishedVersion)
Funders
U.S. National Library of Medicine (R01-LM06916)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Keywords
intrinsically disordered proteins, molten globule, random coil, protein conformational change, clusterin, calcineurin, calmodulin, calsequestrin, flexible linkers, eukaryotic proteins, protein structure prediction

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