SOLUTION STRUCTURE OF THE RECOMBINANT HUMAN ONCOPROTEIN P13(MTCP1)

The human oncoprotein p13(MTCP1) is coded by the MTCP1 gene, a gene in volved in chromosomal translocations associated with T-cell prolymphoc ytic leukemia, a rare form of human leukemia with a mature T-cell phen otype. The primary sequence of p13(MTCP1) is highly and only homologou s to that of p14(TCL1), a product coded by the gene TCL1 which is also involved in T-cell prolymphocytic leukemia. These two proteins probab ly represent the first members of a new family of oncogenic proteins. We present the three-dimensional solution structure of the recombinant p13(MTCP1) determined by homonuclear proton two-dimensional NMR metho ds at 600 MHz. After proton resonance assignments, a total of 1253 dis tance restraints and 64 dihedral restraints were collected. The soluti on structure of p13(MTCP1) is presented as a set of 20 DYANA structure s. The rmsd values with respect to the mean structure for the backbone and all heavy atoms for the conformer family are 1.07 +/- 0.19 and 1. 71 +/- 0.17 Angstrom, when the structured core of the protein (residue s 11-103) is considered. The solution structure of p13(MTCP1) consists of an orthogonal beta-barrel, composed of eight antiparallel beta-str ands which present an original arrangement. The two beta-pleated loops which emerge from this barrel might constitute the interaction surfac e with a potential molecular partner.