Somarelli J A, Lee S Y, Skolnick J, Herrera R J
Department of Biological Sciences, OE304, Florida International University, Miami, Florida 33199, USA.
Proteins. 2008 Jul;72(1):197-208. doi: 10.1002/prot.21908.
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.
FK506结合蛋白（FKBPs）是在多种生物体中发现的一类独特的伴侣蛋白。它们执行多种细胞功能，包括蛋白质折叠、细胞因子调节、类固醇受体复合物运输、核酸结合、组蛋白组装以及细胞凋亡调节。这些功能由具有不同三级构象的特定结构域介导。使用穿线/组装/优化（TASSER）方法，预测了23个物种中总共45种FKBPs的三级结构。将这些模型与先前表征的FKBP溶液结构进行比较，并使用预测结构来鉴定同源蛋白组。所得分类可用于推断新发现的FKBPs的功能作用。三维构象表明，该家族在整个进化过程中可能经历了几次修饰，包括N端和C端区域的缺失、FKBP结构域的重复以及整个功能基序的插入。对接模拟表明，FKBP结构域之外的其他序列片段可能调节FKBPs与免疫抑制药物的结合亲和力。对接模型还表明，一部分FKBPs中存在螺旋-环-螺旋（HLH）区域，这可能负责这组蛋白与核酸之间的相互作用。
