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

J 2013

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 et. al.

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

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

Změněno: 25. 2. 2014 13:03, Olga Křížová

Anotace

V originále

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.

Citovat

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.

@article{1166983,
   author = {Byeon, InandJa L and Ahn, Jinwoo and Mitra, Mithun and Byeon, ChangandHyeock and Hercik, Kamil and Hritz, Jozef and Charlton, Lisa M and Levin, Judith G and Gronenborn, Angela M},
   article_location = {LONDON},
   article_number = {May},
   doi = {http://dx.doi.org/10.1038/ncomms2883},
   keywords = {single-stranded DNA; crystal structure; cytidine deaminase},
   language = {eng},
   issn = {2041-1723},
   journal = {NATURE COMMUNICATIONS},
   title = {NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity},
   volume = {4},
   year = {2013}
}

TY  - JOUR
ID  - 1166983
AU  - Byeon, In-Ja L - Ahn, Jinwoo - Mitra, Mithun - Byeon, Chang-Hyeock - Hercik, Kamil - Hritz, Jozef - Charlton, Lisa M - Levin, Judith G - Gronenborn, Angela M
PY  - 2013
TI  - NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity
JF  - NATURE COMMUNICATIONS
VL  - 4
IS  - May
SP  - "nestránkováno"
EP  - "nestránkováno"
PB  - NATURE PUBLISHING GROUP
SN  - 20411723
KW  - single-stranded DNA
KW  - crystal structure
KW  - cytidine deaminase
N2  - 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.
ER  -

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. \textit{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.

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