Backbone dynamics and solution structure refinement of the N-15-labeled human oncogenic protein p13(MTCP1): Comparison with X-ray data

Two related oncogenes, TCL1 and MTCP1, are overexpressed in certain T-cell prolymphocytic leukemias as a result of chromosomal rearrangements that inv olve the translocation of one T-cell receptor gene to either chromosome 14q 32 or Xq28, respectively. The human oncoprotein p13(MTCP1) is coded by the MTCP1 gene and its primary sequence is highly and only homologous to that o f p14(TCL1), the product of TCL1. These two proteins likely represent the f irst members of a new family of oncogenic proteins. A previous model of the three-dimensional solution structure of p13(MTCP1) was determined recently using exclusively homonuclear proton two-dimensional NMR methods and, almo st simultaneously, high-resolution crystal structures of p13(MTCP1) and p14 (TCL1) appeared in the literature. In order to gain more insight into the d etails of the solution structure, we uniformly labeled p13(MTCP1) with nitr ogen-15. The refined structure benefits from 520 additional NOEs, extracted from either N-15-edited 3D experiments or homonuclear 2D NOESY recorded at 800 MHz, and from a nearly complete set of phi angular restraints. Measure ments of N-15 spin relaxation times and heteronuclear N-15{H-1}NOEs at two magnetic field strengths provided additional insights into the dynamics of the protein backbone. On the basis of these new results, a putative binding surface for this particular class of oncogenes is discussed.