The APOBEC-2 crystal structure and functional
implications for the deaminase AID
Courtney Prochnow1*, Ronda Bransteitter1*, Michael G. Klein1, Myron F. Goodman1& Xiaojiang S. Chen1
senger RNA-editing enzyme catalytic (APOBEC) polypeptides,
which deaminates mRNA and single-stranded DNA1,2. Different
APOBEC members use the same deamination activity to achieve
diverse human biological functions. Deamination by an APOBEC
ical for generating high-affinity antibodies3, and deamination by
APOBEC-3 proteins can inhibit retrotransposons and the replica-
tion of retroviruses such as human immunodeficiency virus and
hepatitis B virus4–7. Here we report the crystal structure of APO2.
APO2forms arod-shaped tetramerthatdiffers markedlyfrom the
square-shaped tetramer of thefree 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
and substrate access. The structure suggests how mutations in
patients with hyper-IgM-2 syndrome inactivate AID, resulting in
defective antibody maturation.
We crystallized APO2, which contains amino acid residues
41–224, with four monomers in each asymmetric unit that form a
tetramer with an atypical elongated shape (Fig. 1a). This tetramer
*These authors contributed equally to this work.
1Molecular and Computational Biology, University of Southern California Los Angeles, California 90089, USA.
127 Å52 Å
β β1′ ′
Figure 1 | ThestructureofAPO2. a,TheAPO2tetramerstructure.Ithasan
accession number: 1MQ0), a fntCDA. c, d, The APO2 monomer structure
rotated by 90 degrees, showing the unique features of APO2: the short b19
strand and helices h4 and h6. h4 and h6 dictate how APO2 oligomerizes.
e, The APO2 dimer formed by two monomers (in purple and yellow). Each
has a different conformation for the h1/b1-turn (in red): a loop (L1) and a
hairpin. f, The tetrameric interface, showing the extensive interactions
charged amino acids in h4, h6 and L1) of the interactions at the tetramer
Vol 445|25 January 2007|doi:10.1038/nature05492