Keywords: NCp8, NCp7, Nucleocapsid
Key steps of the HIV-2 replication cycle. Keywords: NCp8, NCp7, Nucleocapsid protein, Nucleic acid chaperone activity, HIV-1, HIV-Background HIV infection in humans can be caused by two viruses: HIV-1 and the less pathogenic HIV-2 [1,2]. HIV-2 is more closely related to SIVMAC and has only limited genome and protein sequence identity with HIV-1. However, HIV1 and HIV-2 share a similar genome organization, virion structure and replication cycle. Like other retroviruses they possess a dimeric genome assembled from two identical RNA sense strands interacting near their 5-ends. In* Correspondence: kasiapw@ibch.poznan.pl Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Pozna, Polandthe mature viral particles and during early steps of the replication cycle the genomic RNA is extensively coated by 2400 copies of the nucleocapsid protein, derived upon proteolysis of Gag precursor polyproteins [3,4]. This structural role is only one of a multitude of functions performed by these proteins. The nucleocapsid domain of Gag and mature nucleocapsid protein (NC) are involved in critical steps of HIV replication, such as primer tRNA annealing, reverse transcription, vRNA dimerization and packaging, virion assembly and proviral integration into host DNA [5-7]. Many of those functions are correlated with the ability of NC to act as a nucleic acid chaperone (NAC). Such chaperone proteins bind nucleic acids with?2014 Pachulska-Wieczorek et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Pachulska-Wieczorek et al. Retrovirology 2014, 11:54 http://www.retrovirology.com/content/11/1/Page 2 ofbroad specificity and facilitate their folding by PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/12711626 destabilizing misfolded, kinetically trapped structures and enabling the formation of the thermodynamically most favored form [6-9]. They do 1-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole not require ATP and their binding is no longer required once the most stable nucleic acid structure is reached [9,10]. The fully processed, mature nucleocapsid proteins of HIV-1 (NCp7) and HIV-2 (NCp8) are tert-Butyl (7-bromoheptyl)carbamate small basic proteins sharing 67 similarity in amino acid sequence (Figure 1). They contain two strictly conserved Cys-X2-Cys-X4-HisX4-Cys (CCHC) zinc finger domains (ZFs) that are linked by a short basic amino acid sequence (linker region). In both proteins the ZFs are flanked by a short C-terminus and basic N-terminal domain. The N-terminal region of NCp8 is markedly shorter than that of NCp7 and consequently NCp8 is a 48-amino acid protein, whereas NCp7 contains 55 aa [11-13]. Except for the structured ZFs, retroviral NC proteins are highly flexible in their free form. However ordering of NCp7 protein structure has been shown upon binding to nucleic acid, where the disordered N-terminus of the protein forms a 310 helix [14,15]. The N-terminal domain PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/21715270 of NCp8 is too short to form similar helix and limited structural information suggests that the NA recognition mechanism for NCp8 is different and the flexible second ZF plays role similar to that of NCp7 N-terminal region [16,17]. Due to the pleiotropic effe.