APOBEC-2 (APO2) belongs to the family of apolipoprotein B mes-
senger RNA-editing enzyme catalytic (APOBEC) polypeptides,
which deaminates mRNA and single-stranded DNA 1,2 . Different
APOBEC members use the same deamination activity to achieve
diverse human biological functions. Deamination by an APOBEC
protein called activation-induced cytidine deaminase (AID) is crit-
ical for generating high-affinity antibodies 3 , and deamination by
APOBEC-3 proteins can inhibit retrotransposons and the replica-
tion of retroviruses such as human immunodeficiency virus and
hepatitis B virus 4–7 . Here we report the crystal structure of APO2.
APO2 forms a rod-shaped tetramer that differs markedly from the
square-shaped tetramer of the free nucleotide cytidine deaminase,
with which APOBEC proteins share considerable sequence homo-
logy. In APO2, two long a-helices of a monomer structure prevent
the formation of a square-shaped tetramer and facilitate forma-
tion of the rod-shaped tetramer via head-to-head interactions of
two APO2 dimers. Extensive sequence homology among APOBEC
family members allows us to test APO2 structure-based predic-
tions using AID. We show that AID deamination activity is
impaired by mutations predicted to interfere with oligomerization
and substrate access. The structure suggests how mutations in
patients with hyper-IgM-2 syndrome inactivate AID, resulting in
defective antibody maturation.
Description
The APOBEC-2 crystal structure and functional implications for the deaminase AID : Abstract : Nature
%0 Journal Article
%1 prochnow2007apobec2
%A Prochnow, Courtney
%A Bransteitter, Ronda
%A Klein, Michael G.
%A Goodman, Myron F.
%A Chen, Xiaojiang S.
%D 2007
%J Nature
%K AID context-dependent-mutation hypermutability mutation_spectrum
%N 7126
%P 447--451
%T The APOBEC-2 crystal structure and functional implications for the deaminase AID
%U http://dx.doi.org/10.1038/nature05492
%V 445
%X APOBEC-2 (APO2) belongs to the family of apolipoprotein B mes-
senger RNA-editing enzyme catalytic (APOBEC) polypeptides,
which deaminates mRNA and single-stranded DNA 1,2 . Different
APOBEC members use the same deamination activity to achieve
diverse human biological functions. Deamination by an APOBEC
protein called activation-induced cytidine deaminase (AID) is crit-
ical for generating high-affinity antibodies 3 , and deamination by
APOBEC-3 proteins can inhibit retrotransposons and the replica-
tion of retroviruses such as human immunodeficiency virus and
hepatitis B virus 4–7 . Here we report the crystal structure of APO2.
APO2 forms a rod-shaped tetramer that differs markedly from the
square-shaped tetramer of the free nucleotide cytidine deaminase,
with which APOBEC proteins share considerable sequence homo-
logy. In APO2, two long a-helices of a monomer structure prevent
the formation of a square-shaped tetramer and facilitate forma-
tion of the rod-shaped tetramer via head-to-head interactions of
two APO2 dimers. Extensive sequence homology among APOBEC
family members allows us to test APO2 structure-based predic-
tions using AID. We show that AID deamination activity is
impaired by mutations predicted to interfere with oligomerization
and substrate access. The structure suggests how mutations in
patients with hyper-IgM-2 syndrome inactivate AID, resulting in
defective antibody maturation.
@article{prochnow2007apobec2,
abstract = {APOBEC-2 (APO2) belongs to the family of apolipoprotein B mes-
senger RNA-editing enzyme catalytic (APOBEC) polypeptides,
which deaminates mRNA and single-stranded DNA 1,2 . Different
APOBEC members use the same deamination activity to achieve
diverse human biological functions. Deamination by an APOBEC
protein called activation-induced cytidine deaminase (AID) is crit-
ical for generating high-affinity antibodies 3 , and deamination by
APOBEC-3 proteins can inhibit retrotransposons and the replica-
tion of retroviruses such as human immunodeficiency virus and
hepatitis B virus 4–7 . Here we report the crystal structure of APO2.
APO2 forms a rod-shaped tetramer that differs markedly from the
square-shaped tetramer of the free nucleotide cytidine deaminase,
with which APOBEC proteins share considerable sequence homo-
logy. In APO2, two long a-helices of a monomer structure prevent
the formation of a square-shaped tetramer and facilitate forma-
tion of the rod-shaped tetramer via head-to-head interactions of
two APO2 dimers. Extensive sequence homology among APOBEC
family members allows us to test APO2 structure-based predic-
tions using AID. We show that AID deamination activity is
impaired by mutations predicted to interfere with oligomerization
and substrate access. The structure suggests how mutations in
patients with hyper-IgM-2 syndrome inactivate AID, resulting in
defective antibody maturation.},
added-at = {2014-07-02T00:21:46.000+0200},
author = {Prochnow, Courtney and Bransteitter, Ronda and Klein, Michael G. and Goodman, Myron F. and Chen, Xiaojiang S.},
biburl = {https://www.bibsonomy.org/bibtex/21b4d3da69ddd2cf0d2a9978842136970/peter.ralph},
comment = {10.1038/nature05492},
description = {The APOBEC-2 crystal structure and functional implications for the deaminase AID : Abstract : Nature},
interhash = {609e4f57730a538edf89817674946097},
intrahash = {1b4d3da69ddd2cf0d2a9978842136970},
issn = {00280836},
journal = {Nature},
keywords = {AID context-dependent-mutation hypermutability mutation_spectrum},
month = jan,
number = 7126,
pages = {447--451},
timestamp = {2014-07-02T00:32:47.000+0200},
title = {The {APOBEC}-2 crystal structure and functional implications for the deaminase {AID}},
url = {http://dx.doi.org/10.1038/nature05492},
volume = 445,
year = 2007
}