Rebelling for a reason: protein structural "outliers".
Analysis of structural variation in domain superfamilies can reveal constraints in protein evolution which aids protein structure prediction and classification. Structure-based sequence alignment of distantly related proteins, organized in PASS2 database, provides clues about structurally conserved regions among different functional families. Some superfamily members show large structural differences which are functionally relevant. This paper analyses the impact of structural divergence on function for multi-member superfamilies, selected from the PASS2 superfamily alignment database. Functional annotations within superfamilies, with structural outliers or 'rebels', are discussed in the context of structural variations. Overall, these data reinforce the idea that functional similarities cannot be extrapolated from mere structural conservation. The implication for fold-function prediction is that the functional annotations can only be inherited with very careful consideration, especially at low sequence identities.
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Gandhi Krishi Vigyana Kendra Campus, Bangalore, India.
Gandhimathi
G
Arumugam
Anu G
AG
Nair
Sridhar
S
Hariharaputran
Sowdhamini
S
Ramanathan
D030562:Databases, Protein; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000145:classification; D016415:Sequence Alignment / Q000379:methods*; D012984:Software
D011506:Proteins