The p66 immature precursor of HIV‐1 reverse transcriptase. Issue 10 (12th May 2014)

• Record Type: Journal Article
• Authors: Sharaf, Naima G.; Poliner, Eric; Slack, Ryan L.; Christen, Martin T.; Byeon, In‐Ja L.; Parniak, Michael A.; Gronenborn, Angela M.; Ishima, Rieko
• Is Part Of: Proteins. Volume 82:Issue 10(2014)
• Page Start: 2343
• Page End: 2352
• Publication Date: 2014-05-12
• Subjects: Proteins -- Periodicals; Proteins -- Periodicals; 572.6
• DOI: 10.1002/prot.24594
• Languages: English
• ISSNs: 0887-3585

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>In contrast to the wealth of structural data available for the mature p66/p51 heterodimeric human immunodeficiency virus type 1 reverse transcriptase (RT), the structure of the homodimeric p66 precursor remains unknown. In all X‐ray structures of mature RT, free or complexed, the processing site in the p66 subunit, for generating the p51 subunit, is sequestered into a β‐strand within the folded ribonuclease H (RNH) domain and is not readily accessible to proteolysis, rendering it difficult to propose a simple and straightforward mechanism of the maturation step. Here, we investigated, by solution NMR, the conformation of the RT p66 homodimer. Our data demonstrate that the RNH and Thumb domains in the p66 homodimer are folded and possess conformations very similar to those in mature RT. This finding suggests that maturation models which invoke a complete or predominantly unfolded RNH domain are unlikely. The present study lays the foundation for further in‐depth mechanistic investigations at the atomic level. Proteins 2014; 82:2343–2352. © 2014 Wiley Periodicals, Inc.</p> </abstract>