1tr4
Solution structure of human oncogenic protein gankyrin
|
OverviewOverview
Human gankyrin (226 residues, 24.4 kDa) is a liver oncoprotein that plays, an important role in the development of human hepatocellular carcinomas., In this paper, its solution structure is reported, which is the largest, ankyrin protein ever determined by NMR. The highly degenerate primary, sequences of the seven ankyrin repeats presented a major challenge, which, was overcome by combined use of TROSY experiments, perdeuterated samples, isotope-filtered NMR experiments, and residual dipolar couplings. The, final structure was of high quality, with atomic rmsds for the backbone, (N, C', and C(alpha)) and all heavy atoms (residues 4-224) of 0.69 +/-, 0.09 and 1.04 +/- 0.09 A, respectively. Detailed analyses of NMR data, suggested that the conserved TPLH motifs play important structural roles, in stabilizing the repeating ankyrin scaffold. Gankyrin is, conformationally more stable than the tumor suppressor p16(INK4A), possibly due to the structural roles of conserved residues evidenced by, slowly exchanging backbone amides as well as hydrogen bonding networks, involving labile side chain protons. Structural comparison with p16(INK4A), identified several residues of gankyrin that are potentially important for, CDK4 binding, whereas observation of the thiol proton of C180 indicated a, well-structured Rb-binding site in the helical region of the sixth ankyrin, repeat. Interestingly, the CDK4-binding site and Rb-binding site located, in N- and C-terminal regions, respectively, are separated by comparatively, more stable ankyrin repeats and highly condensed positive surface charge., These results and analyses will shed light on the structural basis of the, function of human gankyrin.
About this StructureAbout this Structure
1TR4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of the human oncogenic protein gankyrin containing seven ankyrin repeats and analysis of its structure--function relationship., Yuan C, Li J, Mahajan A, Poi MJ, Byeon IJ, Tsai MD, Biochemistry. 2004 Sep 28;43(38):12152-61. PMID:15379554
Page seeded by OCA on Mon Nov 12 19:27:12 2007