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The p66 immature precursor of HIV‐1 reverse transcriptase
Author(s) -
Sharaf Naima G.,
Poliner Eric,
Slack Ryan L.,
Christen Martin T.,
Byeon InJa L.,
Parniak Michael A.,
Gronenborn Angela M.,
Ishima Rieko
Publication year - 2014
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24594
Subject(s) - reverse transcriptase , protein subunit , proteolysis , chemistry , human immunodeficiency virus (hiv) , biology , stereochemistry , computational biology , microbiology and biotechnology , biochemistry , enzyme , rna , virology , gene
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.