A structural-alphabet-based strategy for finding structural motifs across protein families.
Proteins with insignificant sequence and overall structure similarity may still share locally conserved contiguous structural segments; i.e. structural/3D motifs. Most methods for finding 3D motifs require a known motif to search for other similar structures or functionally/structurally crucial residues. Here, without requiring a query motif or essential residues, a fully automated method for discovering 3D motifs of various sizes across protein families with different folds based on a 16-letter structural alphabet is presented. It was applied to structurally non-redundant proteins bound to DNA, RNA, obligate/non-obligate proteins as well as free DNA-binding proteins (DBPs) and proteins with known structures but unknown function. Its usefulness was illustrated by analyzing the 3D motifs found in DBPs. A non-specific motif was found with a 'corner' architecture that confers a stable scaffold and enables diverse interactions, making it suitable for binding not only DNA but also RNA and proteins. Furthermore, DNA-specific motifs present 'only' in DBPs were discovered. The motifs found can provide useful guidelines in detecting binding sites and computational protein redesign.
Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.
Chih Yuan
CY
Wu
Yao Chi
YC
Chen
Carmay
C
Lim
D020816:Amino Acid Motifs; D019295:Computational Biology / Q000379:methods; D004268:DNA-Binding Proteins / Q000737:chemistry; D019077:Helix-Turn-Helix Motifs; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000145:classification
D004268:DNA-Binding Proteins; D011506:Proteins