Coupled folding and binding with α-helix-forming molecular recognition elements

Christopher J. Oldfield, Yugong Cheng, Marc S. Cortese, Pedro Romero, Vladimir N. Uversky, A. Dunker

Research output: Contribution to journalArticle

428 Citations (Scopus)

Abstract

Many protein-protein and protein-nucleic acid interactions involve coupled folding and binding of at least one of the partners. Here, we propose a protein structural element or feature that mediates the binding events of initially disordered regions. This element consists of a short region that undergoes coupled binding and folding within a longer region of disorder. We call these features "molecular recognition elements" (MoREs). Examples of MoREs bound to their partners can be found in the α-helix, β-strand, polyproline II helix, or irregular secondary structure conformations, and in various mixtures of the four structural forms. Here we describe an algorithm that identifies regions having propensities to become α-helix-forming molecular recognition elements (α-MoREs) based on a discriminant function that indicates such regions while giving a low false-positive error rate on a large collection of structured proteins. Application of this algorithm to databases of genomics and functionally annotated proteins indicates that α-MoREs are likely to play important roles protein-protein interactions involved in signaling events.

Original languageEnglish
Pages (from-to)12454-12470
Number of pages17
JournalBiochemistry
Volume44
Issue number37
DOIs
StatePublished - Sep 20 2005

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Molecular recognition
Proteins
Genomics
Nucleic Acids
Conformations
Databases

ASJC Scopus subject areas

  • Biochemistry

Cite this

Oldfield, C. J., Cheng, Y., Cortese, M. S., Romero, P., Uversky, V. N., & Dunker, A. (2005). Coupled folding and binding with α-helix-forming molecular recognition elements. Biochemistry, 44(37), 12454-12470. https://doi.org/10.1021/bi050736e

Coupled folding and binding with α-helix-forming molecular recognition elements. / Oldfield, Christopher J.; Cheng, Yugong; Cortese, Marc S.; Romero, Pedro; Uversky, Vladimir N.; Dunker, A.

In: Biochemistry, Vol. 44, No. 37, 20.09.2005, p. 12454-12470.

Research output: Contribution to journalArticle

Oldfield, CJ, Cheng, Y, Cortese, MS, Romero, P, Uversky, VN & Dunker, A 2005, 'Coupled folding and binding with α-helix-forming molecular recognition elements', Biochemistry, vol. 44, no. 37, pp. 12454-12470. https://doi.org/10.1021/bi050736e
Oldfield CJ, Cheng Y, Cortese MS, Romero P, Uversky VN, Dunker A. Coupled folding and binding with α-helix-forming molecular recognition elements. Biochemistry. 2005 Sep 20;44(37):12454-12470. https://doi.org/10.1021/bi050736e
Oldfield, Christopher J. ; Cheng, Yugong ; Cortese, Marc S. ; Romero, Pedro ; Uversky, Vladimir N. ; Dunker, A. / Coupled folding and binding with α-helix-forming molecular recognition elements. In: Biochemistry. 2005 ; Vol. 44, No. 37. pp. 12454-12470.
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