title: Structural insight into HIV-1 reverse transcription initiation in MAL-like templates (CRF01_AE, subtype G and CRF02_AG).
abstract: Based on the known structural model for reverse transcription initiation complex of the human immunodeficiency virus type 1 (HIV-1) MAL isolate, we attempted to predict a structural behavior of MAL-like templates (CRF01_AE, subtype G and CRF02_AG) within the initiation complex by in silico experiments. Switches from the D-duplex (dimerization-competent) conformation to the I-duplex (initiation-competent) conformation and then to conformations with an open primer activation signal (PAS) structure have been examined for four fragments of U5 and primer binding site (PBS) region, the minimal fragment (nt 121-243), fragment 1 (nt 110-243), fragment 2 (nt 113-259), and extended fragment 2 (nt 109-261). Switches from the D-duplex conformation to the I-duplex conformation in the minimal fragment or fragment 1 and from the I-duplex conformation to conformations with exposed PAS motif in fragment 1 are similar in all MAL-like templates. A PAS exposure in fragment 2 and extended fragment 2 is supported by PBS stem extension which structure is affected by subtype-specific variations in CRF01_AE (the mutated motif (116)GUUAG(120)) and CRF02_AG (7-nt deletion downstream of the PBS motif and G/C/A insertion at the 3' end of fragment 2). These switchable conformations contain the established structural elements essential for HIV-1 reverse transcription initiation as well as several elements that may also be relevant to initiation process, namely hairpins with GAAA apical loops and self-contained motifs of the duplicate insertion and the downstream palindromic sequence. Taken together, our findings suggest a role for the duplicate insertion of MAL-like templates in HIV-1 reverse transcription initiation process and possible mechanisms to realize this role.
authors.affiliation: a Department of Molecular and Quantum Biophysics , Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine , 150 Zabolotnoho Str., 03680 Kyiv , Ukraine.
authors.forename: Irina N
authors.initials: IN
authors.lastname: Kolomiets
authors.forename: Margarita I
authors.initials: MI
authors.lastname: Zarudnaya
authors.forename: Andriy L
authors.initials: AL
authors.lastname: Potyahaylo
authors.forename: Dmytro M
authors.initials: DM
authors.lastname: Hovorun
mesh_terms: D001483:Base Sequence; D003198:Computer Simulation; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000502:physiology*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics*; D055029:Inverted Repeat Sequences; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D048348:Reverse Transcription; D013816:Thermodynamics; D061785:Transcription Initiation, Genetic
chemical_list: C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: HIV-1 reverse transcription initiation; MAL-like templates; PAS (primer activation signal); PBS (primer binding site); secondary structure prediction