NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity

BYEON, In-Ja L, Jinwoo AHN, Mithun MITRA, Chang-Hyeock BYEON, Kamil HERCIK, Jozef HRITZ, Lisa M CHARLTON, Judith G LEVIN a Angela M GRONENBORN. NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity. NATURE COMMUNICATIONS. LONDON: NATURE PUBLISHING GROUP, 2013, roč. 4, May, s. "nestránkováno", 11 s. ISSN 2041-1723. Dostupné z: https://dx.doi.org/10.1038/ncomms2883.

Základní údaje

• Originální název: NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity
• Autoři: BYEON, In-Ja L, Jinwoo AHN, Mithun MITRA, Chang-Hyeock BYEON, Kamil HERCIK, Jozef HRITZ, Lisa M CHARLTON, Judith G LEVIN a Angela M GRONENBORN.
• Vydání: NATURE COMMUNICATIONS, LONDON, NATURE PUBLISHING GROUP, 2013, 2041-1723.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: Genetika a molekulární biologie
• Stát vydavatele: Velká Británie a Severní Irsko
• Utajení: není předmětem státního či obchodního tajemství
• Impakt faktor: Impact factor: 10.742
• Organizační jednotka: Středoevropský technologický institut
• Doi: http://dx.doi.org/10.1038/ncomms2883
• UT WoS: 000320589900086
• Klíčová slova anglicky: single-stranded DNA; crystal structure; cytidine deaminase
• Štítky: ne MU
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

Human APOBEC3A is a single-stranded DNA cytidine deaminase that restricts viral pathogens and endogenous retrotransposons, and has a role in the innate immune response. Furthermore, its potential to act as a genomic DNA mutator has implications for a role in carcinogenesis. A deeper understanding of APOBEC3A's deaminase and nucleic acid-binding properties, which is central to its biological activities, has been limited by the lack of structural information. Here we report the nuclear magnetic resonance solution structure of APOBEC3A and show that the critical interface for interaction with single-stranded DNA substrates includes residues extending beyond the catalytic centre. Importantly, by monitoring deaminase activity in real time, we find that A3A displays similar catalytic activity on APOBEC3A-specific TT (C) under barA- or A3G-specific CC (C) under barA-containing substrates, involving key determinants immediately 5' of the reactive C. Our results afford novel mechanistic insights into APOBEC3A-mediated deamination and provide the structural basis for further molecular studies.