SOLUTION STRUCTURE OF HUMAN P8(MTCP1), A CYSTEINE-RICH PROTEIN ENCODED BY THE MTCP1 ONCOGENE, REVEALS A NEW ALPHA-HELICAL ASSEMBLY MOTIF

MTCP1 (for Mature-T-Cell Proliferation) is the first gene unequivocall y identified in the group of uncommon leukemias with a mature phenotyp e. The three-dimensional solution structure of the human p8(MTCP1) pro tein encoded by the MTCP1 oncogene was determined by homonuclear proto n two-dimensional NMR methods at 600 MHz. After sequence specific assi gnments, a total of 931 distance restraints and 57 dihedral restraints were collected. The location of the three previously unassigned disul fide bridges was determined from preliminary DIANA structures, using a statistical analysis of intercystinyl distances. The solution structu re of p8(MTCP1) is presented as a set of 30 DIANA structures, further refined by restrained molecular dynamics using a simulated annealing p rotocol with the AMBER force field. The r.m.s.d. values with respect t o the mean structure for the backbone and all heavy atoms for a family of 30 structures are 0.73(+-0.28) and 1.17(+/-0.23) Angstrom, when th e structured core of the protein (residues 5 to 63) is considered. The solution structure of p8(MTCP1) reveals an original scaffold consisti ng of three alpha helices, associated with a new cysteine motif. Two o f the helices are covalently paired by two disulfide bridges, forming an alpha-hairpin which resembles an antiparallel coiled-coil. The thir d helix is oriented roughy parallel to the plane defined by the alpha- antiparallel motif and its axis forms an angle of approximate to 60 de grees with respect to the main axis of this motif. (C) 1997 Academic P ress Limited.