Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun:54:8-12.
doi: 10.1016/j.dnarep.2017.03.007. Epub 2017 Mar 28.

Activation-induced deoxycytidine deaminase: Structural basis for favoring WRC hot motif specificities unique among APOBEC family members

Phuong Pham  1 , Samir A Afif  1 , Mayuko Shimoda  2 , Kazuhiko Maeda  3 , Nobuo Sakaguchi  4 , Lars C Pedersen  5 , Myron F Goodman  6
Affiliations

Activation-induced deoxycytidine deaminase: Structural basis for favoring WRC hot motif specificities unique among APOBEC family members

Phuong Pham et al. DNA Repair (Amst). 2017 Jun.
No abstract available

Keywords: AID X-ray crystal structure; Antibody diversity; C-deamination motif selectivity; IgV somatic hypermutation.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Deamination profile of AID, AIDv(Δ15) and Apo3A.
Each colored bar represents a fraction of mutated clones with a C → U deamination at the indicated position on the lacZa sequence (−217 to +149). Red bars identify C deaminations occurring in 5’-WRC hot spot motifs, blue bars represent 5’-SYC cold spot motifs, and green bars represent neutral motifs (neither WRC nor SYC).
Figure 2.
Figure 2.. Comparison of AID-WT and AIDv(Δ15)-induced IgVH SHM in Ramos B-cells.
A) Retroviruses, carrying wild-type AID or AIDv(Δ15) along with the mock control were used to infect Ramos B-cells. After culturing for 2 weeks, IgVH region DNA from infected B-cells was subjected to DNA sequencing analysis. B) Mutation profiles of AID-WT (top) and AIDv(Δ15) (bottom). Horizontal numbered red lines indicate a duplication of the sequences, dotted lines indicate deletion events, solid lines indicate AID WRC hot motifs. Green font indicates IgV CDR regions.
Figure 3.
Figure 3.. Comparison of AID and Apo3A structures.
A) Superposition of crystal structures of Apo3A (green) with DNA bound (yellow) to AIDv(Δ15)(pink). The catalytic zinc ion for AIDv(Δ15) is shown in green and the substrate specificity loop 7 is shown in raspberry. Loop 3 and Loop 7 represent the largest differences in these two structures. B) Closeup of the loop 7 binding pocket for the base at the −1 position to the substrate dC. D131 of Apo3A forms a hydrogen bond to the dT at the −1 position C) Surface rendering of a full atom model of AIDv(Δ15) crystal structure with the DNA from Apo3A superimposed into the active site. Zinc ion is shown in green. The partial cyan atoms are the 18-GIG-23 of the modified loop1 from AIDv(Δ15) with the wild-type residues WAK between I19 and G23 absent. With these residues present the 5’ end of the DNA could differ in position with respect to that of Apo3A. A magenta arrow represents a possible alternative binding position for the 5’ end of the DNA. Mutations in residues labeled in green reduce the processivity of AIDv(Δ15). The surface was calculated using the Adaptive Poisson-Boltzmann Solver tool in PyMol [20].
See this image and copyright information in PMC

References

    1. Pham P, Bransteitter R, Petruska J, Goodman MF, Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation, Nature, 424 (2003) 103–107. - PubMed
    1. MacCarthy T, Kalis SL, Roa S, Pham P, Goodman MF, Scharff MD, Bergman A, V-region mutation in vitro, in vivo, and in silico reveal the importance of the enzymatic properties of AID and the sequence environment, Proc Natl Acad Sci U S A, 106 (2009) 8629–8634. - PMC - PubMed
    1. Beale RC, Petersen-Mahrt SK, Watt IN, Harris RS, Rada C, Neuberger MS, Comparison of the differential context-dependence of DNA deamination by APOBEC enzymes: correlation with mutation spectra in vivo, J Mol Biol, 337 (2004) 585–596. - PubMed
    1. Pham P, Landolph A, Mendez C, Li N, Goodman MF, A Biochemical Analysis Linking APOBEC3A to Disparate HIV-1 Restriction and Skin Cancer, J Biol Chem, 288 (2013) 29294–29304. - PMC - PubMed
    1. Burns MB, Lackey L, Carpenter MA, Rathore A, Land AM, Leonard B, Refsland EW, Kotandeniya D, Tretyakova N, Nikas JB, Yee D, Temiz NA, Donohue DE, McDougle RM, Brown WL, Law EK, Harris RS, APOBEC3B is an enzymatic source of mutation in breast cancer, Nature, 494 (2013) 366–370. - PMC - PubMed

Publication types

Substances