Fu Z Q, Du Bois G C, Song S P, Kulikovskaya I, Virgilio L, Rothstein J L, Croce C M, Weber I T, Harrison R W
Kimmel Cancer Center and Department of Microbiology and Immunology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3413-8. doi: 10.1073/pnas.95.7.3413.
Two related oncogenes, TCL-1 and MTCP-1, are overexpressed in T cell prolymphocytic leukemias as a result of chromosomal rearrangements that involve the translocation of one T cell receptor gene to either chromosome 14q32 or Xq28. The crystal structure of human recombinant MTCP-1 protein has been determined at 2.0 A resolution by using multiwavelength anomalous dispersion data from selenomethionine-enriched protein and refined to an R factor of 0.21. MTCP-1 folds into a compact eight-stranded beta barrel structure with a short helix between the fourth and fifth strands. The topology is unique. The structure of TCL-1 has been predicted by molecular modeling based on 40% amino acid sequence identity with MTCP-1. The identical residues are clustered inside the barrel and on the surface at one side of the barrel. The overall structure of MTCP-1 superficially resembles the structures of proteins in the lipocalin family and calycin superfamily. These proteins have diverse functions, including transport of retinol, fatty acids, chromophores, pheromones, synthesis of prostaglandin, immune modulation, and cell regulation. However, MTCP-1 differs in the topology of the beta strands. The structural similarity suggests that MTCP-1 and TCL-1 form a unique family of beta barrel proteins that is predicted to bind small hydrophobic ligands and function in cell regulation.
两个相关的癌基因TCL-1和MTCP-1，在T细胞原淋巴细胞白血病中由于涉及一个T细胞受体基因易位至14q32或Xq28染色体的染色体重排而过度表达。通过使用来自富含硒代甲硫氨酸的蛋白质的多波长反常色散数据，已在2.0埃分辨率下确定了人重组MTCP-1蛋白的晶体结构，并将其精修至R因子为0.21。MTCP-1折叠成一个紧密的八链β桶状结构，在第四和第五条链之间有一个短螺旋。其拓扑结构是独特的。基于与MTCP-1 40%的氨基酸序列同一性，通过分子建模预测了TCL-1的结构。相同的残基聚集在桶状结构内部和桶状结构一侧的表面。MTCP-1的整体结构表面上类似于脂质运载蛋白家族和杯蛋白超家族中的蛋白质结构。这些蛋白质具有多种功能，包括视黄醇、脂肪酸、发色团、信息素的运输，前列腺素的合成，免疫调节和细胞调节。然而，MTCP-1在β链的拓扑结构上有所不同。结构相似性表明MTCP-1和TCL-1形成了一个独特的β桶状蛋白家族，预计该家族可结合小的疏水性配体并在细胞调节中发挥作用。
