Analysis of molecular recognition features (MoRFs).
Several proteomic studies in the last decade revealed that many proteins are either completely disordered or possess long structurally flexible regions. Many such regions were shown to be of functional importance, often allowing a protein to interact with a large number of diverse partners. Parallel to these findings, during the last five years structural bioinformatics has produced an explosion of results regarding protein-protein interactions and their importance for cell signaling. We studied the occurrence of relatively short (10-70 residues), loosely structured protein regions within longer, largely disordered sequences that were characterized as bound to larger proteins. We call these regions molecular recognition features (MoRFs, also known as molecular recognition elements, MoREs). Interestingly, upon binding to their partner(s), MoRFs undergo disorder-to-order transitions. Thus, in our interpretation, MoRFs represent a class of disordered region that exhibits molecular recognition and binding functions. This work extends previous research showing the importance of flexibility and disorder for molecular recognition. We describe the development of a database of MoRFs derived from the RCSB Protein Data Bank and present preliminary results of bioinformatics analyses of these sequences. Based on the structure adopted upon binding, at least three basic types of MoRFs are found: alpha-MoRFs, beta-MoRFs, and iota-MoRFs, which form alpha-helices, beta-strands, and irregular secondary structure when bound, respectively. Our data suggest that functionally significant residual structure can exist in MoRF regions prior to the actual binding event. The contribution of intrinsic protein disorder to the nature and function of MoRFs has also been addressed. The results of this study will advance the understanding of protein-protein interactions and help towards the future development of useful protein-protein binding site predictors.
Mohan
Amrita
A
School of Informatics, Indiana University, Bloomington, IN 47408, USA.
Oldfield
Christopher J
CJ
Radivojac
Predrag
P
Vacic
Vladimir
V
Cortese
Marc S
MS
Dunker
A Keith
AK
Uversky
Vladimir N
VN
D000465:Algorithms; D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000737:chemistry; D001665:Binding Sites; D002627:Chemistry, Physical / Q000379:methods; D019295:Computational Biology; D003198:Computer Simulation; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D007700:Kinetics; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D012984:Software; D013059:Spectrum Analysis, Raman; D013329:Structure-Activity Relationship
D024322:Amino Acids, Aromatic; D011506:Proteins