Solution structure of human p8MTCP1, 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 unequivocally identified in the group of uncommon leukemias with a mature phenotype. The three-dimensional solution structure of the human p8(MTCP1) protein encoded by the MTCP1 oncogene was determined by homonuclear proton two-dimensional NMR methods at 600 MHz. After sequence specific assignments, a total of 931 distance restraints and 57 dihedral restraints were collected. The location of the three previously unassigned disulfide bridges was determined from preliminary DIANA structures, using a statistical analysis of intercystinyl distances. The solution structure of p8(MTCP1) is presented as a set of 30 DIANA structures, further refined by restrained molecular dynamics using a simulated annealing protocol with the AMBER force field. The r.m.s.d. values with respect to 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) A, when the structured core of the protein (residues 5 to 63) is considered. The solution structure of p8(MTCP1) reveals an original scaffold consisting of three alpha helices, associated with a new cysteine motif. Two of the helices are covalently paired by two disulfide bridges, forming an alpha-hairpin which resembles an antiparallel coiled-coil. The third helix is oriented roughly parallel to the plane defined by the alpha-antiparallel motif and its axis forms an angle of approximately 60 degrees with respect to the main axis of this motif.
Barthe
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P
CNRS-UMR 9955, INSERM-U414, Faculté de Pharmacie, Université de Montpellier I, 15 Avenue Charles Flahault, Montpellier Cedex, 34060, France.
Yang
Y S
YS
Chiche
L
L
Hoh
F
F
Strub
M P
MP
Guignard
L
L
Soulier
J
J
Stern
M H
MH
van Tilbeurgh
H
H
Lhoste
J M
JM
Roumestand
C
C
D003198:Computer Simulation; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009857:Oncogenes; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins / Q000737:chemistry
C082870:MTCP1 protein, human; D011518:Proto-Oncogene Proteins; D003545:Cysteine