5W3V

Crystal Structure of macaque APOBEC3H in complex with RNA

Summary for 5W3V

• Entry DOI: 10.2210/pdb5w3v/pdb
• Descriptor: Apobec3H, RNA (5'-R(P*AP*AP*CP*CP*CP*GP*GP*GP*GP*A)-3'), RNA (5'-R(P*AP*AP*CP*CP*CP*CP*GP*GP*GP*C)-3'), ... (6 entities in total)
• Functional Keywords: cytidine deaminase, protein-rna complex, antiviral protein, antiviral protein-rna complex, antiviral protein/rna
• Biological source: Macaca nemestrina (Pig-tailed macaque); More
• Total number of polymer chains: 8
• Total formula weight: 112154.80

Authors

Bohn, J.A.,Thummar, K.,York, A.,Raymond, A.,Brown, W.C.,Bieniasz, P.D.,Hatziioannou, T.,Smith, J.L. (deposition date: 2017-06-08, release date: 2017-10-25, Last modification date: 2024-10-23)

Primary citation

Bohn, J.A.,Thummar, K.,York, A.,Raymond, A.,Brown, W.C.,Bieniasz, P.D.,Hatziioannou, T.,Smith, J.L.
APOBEC3H structure reveals an unusual mechanism of interaction with duplex RNA.
Nat Commun, 8:1021-1021, 2017

PubMed Abstract: The APOBEC3 family of cytidine deaminases cause lethal hypermutation of retroviruses via deamination of newly reverse-transcribed viral DNA. Their ability to bind RNA is essential for virion infiltration and antiviral activity, yet the mechanisms of viral RNA recognition are unknown. By screening naturally occurring, polymorphic, non-human primate APOBEC3H variants for biological and crystallization properties, we obtained a 2.24-Å crystal structure of pig-tailed macaque APOBEC3H with bound RNA. Here, we report that APOBEC3H forms a dimer around a short RNA duplex and, despite the bound RNA, has potent cytidine deaminase activity. The structure reveals an unusual RNA-binding mode in which two APOBEC3H molecules at opposite ends of a seven-base-pair duplex interact extensively with both RNA strands, but form no protein-protein contacts. CLIP-seq analysis revealed that APOBEC3H preferentially binds to sequences in the viral genome predicted to contain duplexes, a property that may facilitate both virion incorporation and catalytic activity.

PubMed: 29044109
DOI: 10.1038/s41467-017-01309-6

Experimental method

X-RAY DIFFRACTION (2.243 Å)