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Sci Rep. 2018 Feb 12;8(1):2864. doi: 10.1038/s41598-018-21142-1.

Plastic roles of phenylalanine and tyrosine residues of TLS/FUS in complex formation with the G-quadruplexes of telomeric DNA and TERRA.

Author information

1
Institute of Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan.
2
Graduate School of Energy Science, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan.
3
Department of Chemistry, Graduate School of Science, Shizuoka University, 836 Ohya, Suruga, Shizuoka, 422-8529, Japan.
4
Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1241, Japan.
5
Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
6
Institute of Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan. katahira.masato.6u@kyoto-u.ac.jp.
7
Graduate School of Energy Science, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan. katahira.masato.6u@kyoto-u.ac.jp.

Abstract

The length of a telomere is regulated via elongation and shortening processes. Telomeric DNA and telomeric repeat-containing RNA (TERRA), which both contain G-rich repeated sequences, form G-quadruplex structures. Previously, translocated in liposarcoma (TLS) protein, also known as fused in sarcoma (FUS) protein, was found to form a ternary complex with the G-quadruplex structures of telomeric DNA and TERRA. We then showed that the third RGG motif of TLS, the RGG3 domain, is responsible for the complex formation. However, the structural basis for their binding remains obscure. Here, NMR-based binding assaying revealed the interactions in the binary and ternary complexes of RGG3 with telomeric DNA or/and TERRA. In the ternary complex, tyrosine bound exclusively to TERRA, while phenylalanine bound exclusively to telomeric DNA. Thus, tyrosine and phenylalanine each play a central role in the recognition of TERRA and telomeric DNA, respectively. Surprisingly in the binary complexes, RGG3 used both tyrosine and phenylalanine residues to bind to either TERRA or telomeric DNA. We propose that the plastic roles of tyrosine and phenylalanine are important for RGG3 to efficiently form the ternary complex, and thereby regulate the telomere shortening.

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