Analysis of domain-swapped oligomers reveals local sequence preferences and structural imprints at the linker regions and swapped interfaces

• Published in: PloS one Vol. 7; no. 7; p. e39305
• Main Authors: Shingate, Prashant, Sowdhamini, R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.07.2012; Public Library of Science (PLoS)
• Subjects: Algorithms; Alzheimer's disease; Amino acid sequence; Analysis; Bioinformatics; Biology; Databases, Protein; Encephalopathy; Homology; Interfaces; Mutation; Nervous system diseases; Neurodegenerative diseases; Neurological diseases; Oligomerization; Oligomers; Predictions; Protein Multimerization; Protein Structure, Quaternary; Protein Structure, Tertiary; Proteins; Proteins - chemistry; Proteins - genetics; Residues; Sequence Analysis, Protein; Spongiform encephalopathy; Structural members
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0039305

3D domain swapping is an oligomerization process in which structural elements get exchanged between subunits. This mechanism grasped interest of many researchers due to its association with neurodegenerative diseases like Alzheimer's disease, spongiform encephalopathy etc. Despite the biomedical relevance, very little is known about understanding this mechanism. The quest for ruling principles behind this curious phenomenon that could enable early prediction provided an impetus for our bioinformatics studies. A novel method, HIDE, has been developed to find non-domain-swapped homologues and to identify hinge from domain-swapped oligomers. Non-domain-swapped homologues were identified from the protein structural databank for majority of the domain-swapped entries and hinge boundaries could be recognised automatically by means of successive superposition techniques. Different sequence and structural features in domain-swapped proteins and related proteins have also been analysed. The HIDE algorithm was able to identify hinge region in 83% cases. Sequence and structural analyses of hinge and interfaces reveal amino acid preferences and specific conformations of residues at hinge regions, while comparing the domain-swapped and non-domain-swapped states. Interactions differ significantly between regular dimeric interfaces and interface formed at the site of domain-swapped examples. Such preferences of residues, conformations and interactions could be of predictive value.