HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences
HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences
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DOI：
10.1074/jbc.m108417200
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发表时间：
2002-03-01
影响因子：
4.8
通讯作者：
Bernués, J
中科院分区：
文献类型：
--
作者：
Dintilhac, A;Bernués, J
染色质高迁移率基团蛋白1 （HMGB1）是一种非常丰富的保守蛋白，由两个HMG盒结构域和一个高酸性c端结构域组成。从非特异性结合DNA和与各种蛋白质相互作用的能力来看，HMGB1在DNA相关过程中具有多种功能。然而，它的功能作用仍然是争议的主题。利用噬菌体展示方法，我们已经证明HMGB1可以识别几种肽基序。对蛋白质数据库的计算机搜索发现了与已知的与HMGB1相互作用的蛋白质（如p53）的肽同源性，并使我们能够确定新的潜在候选蛋白。其中，转录激活因子如异质核核糖核蛋白K (hnRNP K)，抑制因子如甲基- cpg结合蛋白2 (MeCP2)，共抑制因子如视网膜母细胞瘤易感性蛋白（pRb）和groucho相关基因蛋白1 （Grg1）和5 （Grg5）。对Grg1与HMGB1相互作用的详细分析证实，该结合区域包含与所鉴定的肽之一同源的序列。我们的研究结果使我们提出HMGB1可能通过蛋白质-蛋白质相互作用在几种多功能复合物的稳定和/或组装中发挥核心作用。
The chromatin high mobility group protein 1 (HMGB1) is a very abundant and conserved protein that is structured into two HMG box domains plus a highly acidic C-terminal domain. From the ability to bind DNA nonspecifically and to interact with various proteins, several functions in DNA-related processes have been assigned to HMGB1. Nevertheless, its functional role remains the subject of controversy. Using a phage display approach we have shown that HMGB1 can recognize several peptide motifs. A computer search of the protein data bases found peptide homologies with proteins already known to interact with HMGB1, like p53, and have allowed us to identify new potential candidates. Among them, transcriptional activators like the heterogeneous nuclear ribonucleoprotein K (hnRNP K), repressors like methyl-CpG binding protein 2 (MeCP2), and co-repressors like the retinoblastoma susceptibility protein (pRb) and Groucho-related gene proteins 1 (Grg1) and 5 (Grg5) can be found. A detailed analysis of the interaction of Grg1 with HMGB1 confirmed that the binding region contained the sequence homologous to one of the peptides identified. Our results have led us to propose that HMGB1 may play a central role in the stabilization and/or assembly of several multifunctional complexes through protein-protein interactions.