Coupled folding and binding with alpha-helix-forming molecular recognition elements.
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 alpha-helix, beta-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 alpha-helix-forming molecular recognition elements (alpha-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 alpha-MoREs are likely to play important roles protein-protein interactions involved in signaling events.
Oldfield
Christopher J
CJ
Molecular Kinetics Inc., 6201 La Pas Trail, Suite 160, Indianapolis, Indiana 46268, USA.
Cheng
Yugong
Y
Cortese
Marc S
MS
Romero
Pedro
P
Uversky
Vladimir N
VN
Dunker
A Keith
AK
D001665:Binding Sites; D030562:Databases, Protein; D007700:Kinetics; D008958:Models, Molecular; D008962:Models, Theoretical; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D011506:Proteins