Crystal structure of the CDK4/6 inhibitory protein p18INK4c provides insights into ankyrin-like repeat structure/function and tumor-derived p16INK4 mutations
Crystal structure of the CDK4/6 inhibitory protein p18INK4c provides insights into ankyrin-like repeat structure/function and tumor-derived p16INK4 mutations
复制标题
CDK4/6 抑制蛋白 p18INK4c 的晶体结构提供了对锚蛋白样重复结构/功能和肿瘤衍生的 p16INK4 突变的深入了解
DOI：
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
R. Marmorstein
中科院分区：
文献类型：
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作者：
R. Venkataramani;K. Swaminathan;R. Marmorstein
p18 INK 4c是INK 4蛋白家族的成员，其功能是通过抑制细胞周期蛋白依赖性激酶4和6的活性来阻止G1至S细胞周期转变。人p18 INK 4c蛋白的X射线晶体结构分辨率为1.95 nm，显示了一个由5个连续的32或33个残基的锚定样重复单元组成的细长分子。每个锚定蛋白样重复序列含有β链螺旋-转角-螺旋延伸链β链基序，其通过β折叠和螺旋束相互作用与相邻基序缔合。保守的锚蛋白样重复残基的功能是促进锚蛋白重复折叠和相邻重复单元之间的三级相互作用。在INK 4蛋白中保守的并且映射到肿瘤来源的p16 INK 4突变的位置的大百分比的残基在蛋白质稳定性中起重要作用。这些残基的一个子集建议INK 4的细胞周期蛋白依赖性激酶4和6的结合表面。该表面以显示出非锚样重复单元特征的结构特征的区域为中心。
p18INK4c is a member of a family of INK4 proteins that function to arrest the G1 to S cell cycle transition by inhibiting the activity of the cyclin-dependent kinases 4 and 6. The X-ray crystal structure of the human p18INK4c protein to a resolution of 1.95 Å reveals an elongated molecule comprised of five contiguous 32- or 33-residue ankyrin-like repeat units. Each ankyrin-like repeat contains a β-strand helix-turn-helix extended strand β-strand motif that associates with neighboring motifs through β-sheet, and helical bundle interactions. Conserved ankyrin-like repeat residues function to facilitate the ankyrin repeat fold and the tertiary interactions between neighboring repeat units. A large percentage of residues that are conserved among INK4 proteins and that map to positions of tumor-derived p16INK4 mutations play important roles in protein stability. A subset of these residues suggest an INK4 binding surface for the cyclin-dependent kinases 4 and 6. This surface is centered around a region that shows structural features uncharacteristic of ankyrin-like repeat units.
影响因子：
10.5
作者：
GUAN, KL;JENKINS, CW;XIONG, Y
通讯作者：
XIONG, Y
影响因子：
56.9
作者：
KAMB, A;GRUIS, NA;SKOLNICK, MH
通讯作者：
SKOLNICK, MH