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Structural plasticity of substrate selection by activation‐induced cytidine deaminase as a regulator of its genome‐wide mutagenic activity
Author(s) -
King Justin J.,
Larijani Mani
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13962
Subject(s) - cytidine deaminase , activation induced (cytidine) deaminase , somatic hypermutation , apobec , rna , dna , biology , biochemistry , chemistry , genetics , genome , gene , b cell , antibody
Activation‐induced cytidine deaminase (AID) mediates somatic hypermutation and class‐switch recombination of antibodies. Computational‐biochemical and crystallography analyses of AID have identified three surface grooves for binding single‐stranded DNA (ssDNA). Functional studies have also found evidence for RNA‐binding motifs on AID. Although AID and the related apolipoprotein B mRNA‐editing enzyme catalytic polypeptide‐like (APOBEC) enzymes share a conserved core, AID uniquely features multiple substrate‐binding motifs on its surface. Here we suggest that combinatorial deployment of AID's multiple ssDNA‐ or RNA‐binding motifs yields many substrate‐binding modes that can accommodate ssDNA, RNA, or DNA/RNA substrates of diverse structures. We also suggest that AID oligomerization generates yet additional novel substrate‐binding modes. We propose that this plasticity in substrate choice is an evolved aspect of AID's structure that contributes to the regulation of its differential mutagenic activity at various loci.