Structural biology on the interaction between archaeal CMG helicase and DNA polymerase D

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06081
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: University of Yamanashi
• Principal Investigator: OYAMA Takuji 山梨大学, 大学院総合研究部, 准教授 (60423133)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: DNA複製 / CMGヘリカーゼ / 超好熱古細菌 / 結晶構造解析

Outline of Final Research Achievements

In the early stage of DNA replication, the CMG complex, comprising a MCM helicase core (hexamer) and two activators GINS (tetramer) and Cdc45 (GAN in archaea), unwinds the template DNA. Archaea have a DNA replication mechanism similar to that of eukaryotes, and we have recently found a novel interaction between (1) CMG, which is shared among archaea and eukaryotes, and (2) DNA polymerase D, which is unique to archaea. In order to elucidate the functional importance of the new complex interaction revealed by biochemical analysis, we performed X-ray crystallography of a partial complex containing the functional interaction. We succeeded in reconstructing and determining the crystal structure of the complex, elucidated the details of the interaction at the amino acid level, and confirmed the importance of the interaction by biochemical analysis.

Free Research Field

構造生物化学

Academic Significance and Societal Importance of the Research Achievements

古細菌が持つDNA複製に関わるタンパク質の構造と機能は、真核生物由来のものに似ており、複合体はしばしば簡略化されているため、ヒトを含む真核生物の複雑なシステムを理解するための有用なモデルである。超好熱古細菌由来タンパク質は熱安定性に優れ、構造解析に有利である。一方、古細菌は他生物界と異なる独自システムも併せ持ち、構造生物学的に興味深い。本研究でターゲットとしたDNAポリメラーゼDは古細菌固有酵素であるが、古細菌としてのユニークな特性に加え、構造機能解析を通して真核生物システムとの類似性を見出せれば、学術的に意義高く、生物種間の進化上の関連まで視野を広げれば、知の蓄積の観点で社会的意義に富む。