W0035

Crystal Structure of Oncogene Product MTCP-1, Solved by MAD Phasing. Z.Q. FU, G.C. DuBois, S.P. Song, I. Kulikovskaya, L. Virgilio, J.L. Rothstein, C.M. Croce, I.T. Weber and R.W. Harrison, Kimmel Cancer Center and Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107 USA

Chromosomal rearrangements in the T cell malignancies observed in T cell prolymphocytic leukemias (T-PLL), and in patients with Ataxia telangiectasia involve the translocation of one T cell receptor gene to either chromosome 14q32 or Xq28. These genetic aberrations juxtapose cellular protooncogenes to enhancer elements leading to deregulation of oncogene expression. The two oncogenes involved in these translocations are MTCP-1 and TCL-1, which constitute a novel family of genes involved in lymphoid proliferation and T cell malignancies.

The crystal structure of human recombinant MTCP-1 protein has been determined at 2.0 anstrangs by using MAD (multiwavelength anomalous dispersion) data from selenomethionine enriched protein, and refined to an R-factor 0f 0.21 (R-free of 0.25). MTCP-1 folds into a compact 8-stranded beta barrel structure with a short helix between the fourth and fifth strands. The topology is unique. 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 secondary structure. A model structure of TCL-1 has been predicted by homology modeling based on 40% amino acid sequence identity, and 61% similarity with MTCP-1.