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.