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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Mol+Biol
2016 ; 428
(23
): 4626-4638
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Biochemical Characterization of APOBEC3H Variants: Implications for Their HIV-1
Restriction Activity and mC Modification
#MMPMID27534815
Gu J
; Chen Q
; Xiao X
; Ito F
; Wolfe A
; Chen XS
J Mol Biol
2016[Nov]; 428
(23
): 4626-4638
PMID27534815
show ga
APOBEC3H (A3H) is the most polymorphic member of the APOBEC3 family. Seven
haplotypes (hap I-VII) and four mRNA splicing variants (SV) of A3H have been
identified. The various haplotypes differ in anti-HIV activity, which is
attributed to differences in protein stability, subcellular distribution, and/or
RNA binding and virion packaging. Here, we report the first comparative
biochemical studies of all the A3H variants using highly purified proteins. We
show that all haplotypes were stably expressed and could be purified to
homogeneity by Escherichia coli expression. Surprisingly, four out of the seven
haplotypes showed high cytosine (C) deaminase activity, with hap V displaying
extremely high activity that was comparable to the highly active A3A.
Furthermore, all four haplotypes that were active in C deamination were also
highly active on methylated C (mC), with hap II displaying almost equal
deamination efficiency on both. The deamination activity of these A3H variants
correlates well with their reported anti-HIV activity for the different
haplotypes, suggesting that deaminase activity may be an important factor in
determining their respective anti-HIV activities. Moreover, mC deamination of A3H
displayed a strong preference for the sequence motif of T-mCpG-C/G, which may
suggest a potential role in genomic mC modification at the characteristic "CpG"
island motif.