%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 }