Intrinsically disordered protein

A. Dunker, J. David Lawson, Celeste J. Brown, Ryan M. Williams, Pedro Romero, Jeong S. Oh, Christopher J. Oldfield, Andrew M. Campen, Catherine M. Ratliff, Kerry W. Hipps, Juan Ausio, Mark S. Nissen, Raymond Reeves, ChulHee Kang, Charles R. Kissinger, Robert W. Bailey, Michael D. Griswold, Wah Chiu, Ethan C. Garner, Zoran Obradovic

Research output: Contribution to journalArticle

1473 Citations (Scopus)

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 ≥ 50 consecutive residues.

Original languageEnglish (US)
Pages (from-to)26-59
Number of pages34
JournalJournal of Molecular Graphics and Modelling
Volume19
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Intrinsically Disordered Proteins
proteins
Proteins
disorders
Molten materials
Calcineurin
Calmodulin
calmodulin
Order disorder transitions
Nucleosomes
Amino acids
Calcium
helices
amino acids
calcium
Calsequestrin
sarcoplasmic reticulum
Ions
Clusterin
Protein folding

Keywords

  • Disordered protein
  • Function
  • Genomics
  • Molten globules
  • Phase changes
  • Proteomics
  • Random coils
  • Structure

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Spectroscopy
  • Atomic and Molecular Physics, and Optics

Cite this

Dunker, A., Lawson, J. D., Brown, C. J., Williams, R. M., Romero, P., Oh, J. S., ... Obradovic, Z. (2001). Intrinsically disordered protein. Journal of Molecular Graphics and Modelling, 19(1), 26-59. https://doi.org/10.1016/S1093-3263(00)00138-8

Intrinsically disordered protein. / Dunker, A.; 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.

In: Journal of Molecular Graphics and Modelling, Vol. 19, No. 1, 2001, p. 26-59.

Research output: Contribution to journalArticle

Dunker, A, Lawson, JD, Brown, CJ, Williams, RM, Romero, P, Oh, JS, Oldfield, CJ, Campen, AM, Ratliff, CM, Hipps, KW, Ausio, J, Nissen, MS, Reeves, R, Kang, C, Kissinger, CR, Bailey, RW, Griswold, MD, Chiu, W, Garner, EC & Obradovic, Z 2001, 'Intrinsically disordered protein', Journal of Molecular Graphics and Modelling, vol. 19, no. 1, pp. 26-59. https://doi.org/10.1016/S1093-3263(00)00138-8
Dunker, A. ; 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. / Intrinsically disordered protein. In: Journal of Molecular Graphics and Modelling. 2001 ; Vol. 19, No. 1. pp. 26-59.
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AU - Oh, Jeong S.

AU - Oldfield, Christopher J.

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AU - Bailey, Robert W.

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AU - Obradovic, Zoran

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N2 - 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 ≥ 50 consecutive residues.

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