4月18日,，美國(guó)科學(xué)院院報(bào)PNAS在線發(fā)表了生物物理研究所劉迎芳研究員實(shí)驗(yàn)室與美國(guó)阿拉巴馬大學(xué)Igor Chesnokov博士的合作研究成果，文章題目為：Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB,。這一文章中報(bào)導(dǎo)了他們對(duì)DNA復(fù)制起始復(fù)合體（Origin recognition complex, ORC）中Orc6亞基的結(jié)構(gòu)生物學(xué)研究成果。通過對(duì)Orc6的結(jié)構(gòu)生物學(xué)研究，他們揭示了人Orc6蛋白可以直接結(jié)合DNA，并且這一DNA結(jié)合能力對(duì)ORC復(fù)合體識(shí)別復(fù)制起始位點(diǎn)以及啟動(dòng)DNA復(fù)制必不可少,。該文章第一作者為我所的劉世軒博士。
圖解：人Orc6亞基的結(jié)構(gòu)（ (A) Structure of human Orc6 helical domain; (B)Superimpose of Orc6 to TFIIB-DNA complex. Orc6 helical domain is shown in color blue, TFIIB is shown in grey and double-stranded DNA is color in gold. The three residues, K168, Q129 and R137 of Orc6, that are involved in DNA binding are shown in magenta.）（生物谷Bioon.com）
生物谷推薦原文出處：
PNAS doi: 10.1073/pnas.1013676108
Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB
Shixuan Liua, Maxim Balasovb, Hongfei Wanga, Lijie Wua, Igor N. Chesnokovb,1, and Yingfang Liua,1
Abstract
The Origin Recognition Complex (ORC) is a six-subunit protein important for the initiation of DNA replication in eukaryotic cells. Orc6 is the smallest and the least conserved among ORC subunits. It is required for the DNA replication but also has a function in cytokinesis in metazoan species, however, the mechanisms of Orc6 action in these processes are not clear. Here we report a structure of the middle domain of human Orc6. This domain has an overall fold similar to the corresponding helical domain of transcription factor TFIIB. Based on these findings, a model of Orc6 binding to DNA is produced. We have identified amino acids of Orc6 which are directly involved in DNA binding. Alterations of these amino acids abolish DNA binding ability of Orc6 and also result in reduced levels of DNA replication in vitro and in cultured cells. Our data indicate that Orc6 is one of the DNA binding subunits of ORC in metazoan species. We propose that Orc6 may participate in positioning of ORC at the origins of DNA replication similar to the role of TFIIB in positioning transcription preinitiation complex at the promoter.
