6BUX

CRYSTAL STRUCTURE OF APOBEC3G CATALYTIC DOMAIN COMPLEX WITH SUBSTRATE SSDNA

Summary for 6BUX

• Entry DOI: 10.2210/pdb6bux/pdb
• Descriptor: Apolipoprotein B mRNA editing enzyme catalytic subunit 3G catalytic domain, DNA (5'-D(*AP*AP*TP*CP*CP*CP*AP*AP*A)-3'), ZINC ION, ... (5 entities in total)
• Functional Keywords: hydrolase, antiviral defence, dna cytidine deaminase, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 25912.41

Authors

Maiti, A.,Matsuo, H. (deposition date: 2017-12-11, release date: 2018-07-18, Last modification date: 2023-10-04)

Primary citation

Maiti, A.,Myint, W.,Kanai, T.,Delviks-Frankenberry, K.,Sierra Rodriguez, C.,Pathak, V.K.,Schiffer, C.A.,Matsuo, H.
Crystal structure of the catalytic domain of HIV-1 restriction factor APOBEC3G in complex with ssDNA.
Nat Commun, 9:2460-2460, 2018

PubMed Abstract: 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 Å 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.

PubMed: 29941968
DOI: 10.1038/s41467-018-04872-8

Experimental method

X-RAY DIFFRACTION (1.856 Å)