Structural highlights
Publication Abstract from PubMed
The human APOBEC3G protein is a cytidine deaminase that generates cytidine to deoxy-uridine mutations in single-stranded DNA (ssDNA), and capable of restricting replication of HIV-1 by generating mutations in viral genome. The mechanism by which APOBEC3G specifically deaminates 5'-CC motifs has remained elusive since structural studies have been hampered due to apparently weak ssDNA binding of the catalytic domain of APOBEC3G. We overcame the problem by generating a highly active variant with higher ssDNA affinity. Here, we present the crystal structure of this variant complexed with a ssDNA substrate at 1.86 A resolution. This structure reveals atomic-level interactions by which APOBEC3G recognizes a functionally-relevant 5'-TCCCA sequence. This complex also reveals a key role of W211 in substrate recognition, implicating a similar recognition in activation-induced cytidine deaminase (AID) with a conserved tryptophan.
Crystal structure of the catalytic domain of HIV-1 restriction factor APOBEC3G in complex with ssDNA.,Maiti A, Myint W, Kanai T, Delviks-Frankenberry K, Sierra Rodriguez C, Pathak VK, Schiffer CA, Matsuo H Nat Commun. 2018 Jun 25;9(1):2460. doi: 10.1038/s41467-018-04872-8. PMID:29941968[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Maiti A, Myint W, Kanai T, Delviks-Frankenberry K, Sierra Rodriguez C, Pathak VK, Schiffer CA, Matsuo H. Crystal structure of the catalytic domain of HIV-1 restriction factor APOBEC3G in complex with ssDNA. Nat Commun. 2018 Jun 25;9(1):2460. doi: 10.1038/s41467-018-04872-8. PMID:29941968 doi:http://dx.doi.org/10.1038/s41467-018-04872-8
