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Structure‐based classification of 45 FK506‐binding proteins
Author(s) -
Somarelli J. A.,
Lee S. Y.,
Skolnick J.,
Herrera R. J.
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21908
Subject(s) - fkbp , docking (animal) , computational biology , threading (protein sequence) , biology , nucleic acid , protein superfamily , protein folding , structural motif , protein structure , biochemistry , chemistry , gene , medicine , nursing
The FK506‐binding proteins (FKBPs) are a unique group of chaperones found in a wide variety of organisms. They perform a number of cellular functions including protein folding, regulation of cytokines, transport of steroid receptor complexes, nucleic acid binding, histone assembly, and modulation of apoptosis. These functions are mediated by specific domains that adopt distinct tertiary conformations. Using the Threading/ASSEmbly/Refinement (TASSER) approach, tertiary structures were predicted for a total of 45 FKBPs in 23 species. These models were compared with previously characterized FKBP solution structures and the predicted structures were employed to identify groups of homologous proteins. The resulting classification may be utilized to infer functional roles of newly discovered FKBPs. The three‐dimensional conformations revealed that this family may have undergone several modifications throughout evolution, including loss of N‐ and C‐terminal regions, duplication of FKBP domains as well as insertions of entire functional motifs. Docking simulations suggest that additional sequence segments outside FKBP domains may modulate the binding affinity of FKBPs to immunosuppressive drugs. The docking models also indicate the presence of a helix‐loop‐helix (HLH) region within a subset of FKBPs, which may be responsible for the interaction between this group of proteins and nucleic acids. Proteins 2008. © 2008 Wiley‐Liss, Inc.