Structural plasticity of substrate selection by activation-induced cytidine deaminase as a regulator of its genome-wide mutagenic activity.
FEBS Lett
; 595(1): 3-13, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33089497
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genoma Humano
/
Citidina Desaminase
/
Mutagênicos
Limite:
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá