Crystal structures of Tcl1 family oncoproteins and their conserved surface features.
Members of the TCL1 family of oncogenes are abnormally expressed in mature T-cell leukemias and B-cell lymphomas. The proteins are involved in the coactivation of protein kinase B (Akt/PKB), a key intracellular kinase. The sequences and crystal structures of three Tcl1 proteins were analyzed in order to understand their interactions with Akt/PKB and the implications for lymphocyte malignancies. Tcl1 proteins are approximately 15 kD and share 25-80% amino acid sequence identity. The tertiary structures of mouse Tcl1, human Tcl1, and Mtcp1 are very similar. Analysis of the structures revealed conserved semi-planar surfaces that have characteristics of surfaces involved in protein-protein interactions. The Tcl1 proteins show differences in surface charge distribution and oligomeric state suggesting that they do not interact in the same way with Akt/PKB and other cellular protein(s).
Petock
John M
JM
Department of Biology, Georgia State University, Atlanta, GA, USA. biojmp@langate.gsu.edu
Torshin
Ivan Y
IY
Wang
Yuan-Fang
YF
Du Bois
Garrett C
GC
Croce
Carlo M
CM
Harrison
Robert W
RW
Weber
Irene T
IT
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000737:chemistry*; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000737:chemistry*
D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human; C490393:Tcl1 protein, mouse; D014157:Transcription Factors