Structural basis of G-quadruplex recognition by TLS protein which lead to telomere lengthening

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14636
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Kondo Keiko 京都大学, エネルギー理工学研究所, 研究員 (00707474)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: NMR / 四重鎖核酸 / 核酸結合蛋白質 / 天然変性蛋白質

Outline of Final Research Achievements

Interaction of telomeric DNA and TERRA with peptide motifs in TLS, where tyrosine residue or phenylalanine residue is flanked with two RGG motifs, were analyzed by NMR. The peptide motif was suggested to bind to a G-tetrad and a loop region on the G-tetrad of telomeric DNA. On the other hand, it mainly bound to G-tetrads of TERRA. Additionally, the peptide motif was turned out to be able to interact with DNA-RNA hybrid quadruplex that formed by telomeric DNA and TERRA. Furthermore, conformational change of TLS from closed form to open form on binding telomeric DNA or TERRA was revealed.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

TLSは細胞核内において遺伝子発現制御をはじめとする種々の制御に関与する核酸結合蛋白質であり、その機能不全は神経疾患をもたらすことも知られている。しかし、その核酸結合の機構は十分には明らかにされていない。本研究において得られたTLSと四重鎖核酸との結合に関する知見、および核酸との結合がTLSに構造変化をもたらすという知見は、生体内におけるTLSの機能を解明し、遺伝子発現制御などの普遍的な生命現象への理解を深めることに繋がる。