1BU9

SOLUTION STRUCTURE OF P18-INK4C, 21 STRUCTURES

1BU9 の概要

• エントリーDOI: 10.2210/pdb1bu9/pdb
• 分子名称: PROTEIN (CYCLIN-DEPENDENT KINASE 6 INHIBITOR) (1 entity in total)
• 機能のキーワード: cell cycle inhibitor, p18ink4c, tumor, suppressor, cyclin-dependent kinase, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18149.36

構造登録者

Byeon, I.-J.L.,Li, J.,Tsai, M.-D. (登録日: 1998-09-15, 公開日: 1999-09-13, 最終更新日: 2023-12-27)

主引用文献

Li, J.,Byeon, I.J.,Ericson, K.,Poi, M.J.,O'Maille, P.,Selby, T.,Tsai, M.D.
Tumor suppressor INK4: determination of the solution structure of p18INK4C and demonstration of the functional significance of loops in p18INK4C and p16INK4A.
Biochemistry, 38:2930-2940, 1999

PubMed Abstract: Since the structures of several ankyrin-repeat proteins including the INK4 (inhibitor of cyclin-dependent kinase 4) family have been reported recently, the detailed structures and the functional roles of the loops have drawn considerable interest. This paper addresses the potential importance of the loops of ankyrin-repeat proteins in three aspects. First, the solution structure of p18INK4C was determined by NMR, and the loop structures were analyzed in detail. The loops adapt nascent antiparallel beta-sheet structures, but the positions are slightly different from those in the crystal structure. A detailed comparison between the solution structures of p16 and p18 has also been presented. The determination of the p18 solution structure made such detailed comparisons possible for the first time. Second, the [1H,15N]HSQC NMR experiment was used to probe the interactions between p18INK4C and other proteins. The results suggest that p18INK4C interacts very weakly with dna K and glutathione S-transferase via the loops. The third aspect employed site-specific mutagenesis and functional assays. Three mutants of p18 and 11 mutants of p16 were constructed to test functional importance of loops and helices. The results suggest that loop 2 is likely to be part of the recognition surface of p18INK4C or p16INK4A for CDK4, and they provide quantitative functional contributions of specific residues. Overall, our results enhance understanding of the structural and functional roles of the loops in INK4 tumor suppressors in particular and in ankyrin-repeat proteins in general.

PubMed: 10074345
DOI: 10.1021/bi982286e

実験手法

SOLUTION NMR