1TR4

Solution structure of human oncogenic protein gankyrin

1TR4 の概要

• エントリーDOI: 10.2210/pdb1tr4/pdb
• 分子名称: 26S proteasome non-ATPase regulatory subunit 10 (1 entity in total)
• 機能のキーワード: gankyrin, oncoprotein, ankyrin repeats, protein structure, unknown function
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: O75832
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24459.85

構造登録者

Yuan, C.,Li, J.,Mahajan, A.,Poi, M.J.,Byeon, I.J.,Tsai, M.D. (登録日: 2004-06-19, 公開日: 2004-11-16, 最終更新日: 2024-05-22)

主引用文献

Yuan, C.,Li, J.,Mahajan, A.,Poi, M.J.,Byeon, I.J.,Tsai, M.D.
Solution structure of the human oncogenic protein gankyrin containing seven ankyrin repeats and analysis of its structure--function relationship.
Biochemistry, 43:12152-12161, 2004

PubMed Abstract: 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.

PubMed: 15379554
DOI: 10.1021/bi049116o

実験手法

SOLUTION NMR