羟脯氨酸
丝氨酸
化学
组氨酸
脯氨酸
丙氨酸
细胞生物学
磷酸化
生物化学
信号转导
泛素
肽
蛋白质结构
生物物理学
立体化学
生物
氨基酸
基因
作者
Jung-Hyun Min,Haifeng Yang,Mircea Ivan,Frank B. Gertler,William G. Kaelin,Nikola P. Pavletich
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2002-06-07
卷期号:296 (5574): 1886-1889
被引量:696
标识
DOI:10.1126/science.1073440
摘要
The ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel–Lindau tumor suppressor (pVHL) plays a central role in the cellular response to changes in oxygen availability. pVHL binds to HIF only when a conserved proline in HIF is hydroxylated, a modification that is oxygen-dependent. The 1.85 angstrom structure of a 20-residue HIF-1α peptide–pVHL–ElonginB–ElonginC complex shows that HIF-1α binds to pVHL in an extended β strand–like conformation. The hydroxyproline inserts into a gap in the pVHL hydrophobic core, at a site that is a hotspot for tumorigenic mutations, with its 4-hydroxyl group recognized by buried serine and histidine residues. Although the β sheet–like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling.
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