title: Crystal structure of human multiple copies in T-cell lymphoma-1 oncoprotein.
abstract: Overexpression of multiple copies in T-cell lymphoma-1 (MCT-1) oncogene accompanies malignant phenotypic changes in human lymphoma cells. Specific disruption of MCT-1 results in reduced tumorigenesis, suggesting a potential for MCT-1-targeted therapeutic strategy. MCT-1 is known as a cap-binding protein and has a putative RNA-binding motif, the PUA-domain, at its C-terminus. We determined the crystal structure of apo MCT-1 at 1.7 Å resolution using the surface entropy reduction method. Notwithstanding limited sequence identity to its homologs, the C-terminus of MCT-1 adopted a typical PUA-domain fold that includes secondary structural elements essential for RNA recognition. The surface of the N-terminal domain contained positively charged patches that are predicted to contribute to RNA-binding.
authors.affiliation: Structural Genomics Consortium, 101 College Street, MaRS South Tower, Toronto, Ontario, Canada.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tempel
authors.forename: Slav
authors.initials: S
authors.lastname: Dimov
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Tong
authors.forename: Hee-Won
authors.initials: HW
authors.lastname: Park
authors.forename: Bum Soo
authors.initials: BS
authors.lastname: Hong
mesh_terms: D000409:Alanine / Q000737:chemistry / Q000235:genetics; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D055592:Biophysical Phenomena; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003001:Cloning, Molecular; D003461:Crystallography / Q000379:methods; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D019277:Entropy; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation; D015513:Oncogene Proteins / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016601:RNA-Binding Proteins / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D055672:Static Electricity; D013696:Temperature
chemical_list: D018797:Cell Cycle Proteins; D018076:DNA, Complementary; C115081:MCTS1 protein, human; D015513:Oncogene Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D000409:Alanine