Crystal structure of the endonuclease domain encoded by the telomere-specific long interspersed nuclear element, TRAS1.
The telomere-specific long interspersed nuclear element, TRAS1, encodes an endonuclease domain, TRAS1-EN, which specifically cleaves the telomeric repeat targets (TTAGG)n of insects and (TTAGGG)n of vertebrates. To elucidate the sequence-specific recognition properties of TRAS1-EN, we determined the crystal structure at 2.4-A resolution. TRAS1-EN has a four-layered alpha/beta sandwich structure; its topology is similar to apurinic/apyrimidinic endonucleases, but the beta-hairpin (beta10-beta11) at the edge of the DNA-binding surface makes an extra loop that distinguishes TRAS1-EN from cellular apurinic/apyrimidinic endonucleases. A protein-DNA complex model suggests that the beta10-beta11 hairpin fits into the minor groove, enabling interaction with the telomeric repeats. Mutational studies of TRAS1-EN also indicated that the Asp-130 and beta10-beta11 hairpin structure are involved in specific recognition of telomeric repeats.
Maita
Nobuo
N
Department of Biochemistry, National Institute of Agrobiological Sciences, Tsukuba, 305-8602, Japan.
Anzai
Tomohiro
T
Aoyagi
Hideyuki
H
Mizuno
Hiroshi
H
Fujiwara
Haruhiko
H
D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry; D001483:Base Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray / Q000379:methods; D004247:DNA / Q000737:chemistry; D004252:DNA Mutational Analysis; D004583:Electrons; D004720:Endonucleases / Q000737:chemistry*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D016615:Telomere / Q000737:chemistry / Q000648:ultrastructure
D009841:Oligonucleotides; D001224:Aspartic Acid; D004247:DNA; D004720:Endonucleases; D008274:Magnesium