title: Highly conserved structural properties of the C-terminal tail of HIV-1 gp41 protein despite substantial sequence variation among diverse clades: implications for functions in viral replication.
abstract: Although the HIV-1 Env gp120 and gp41 ectodomain have been extensively characterized in terms of structure and function, similar characterizations of the C-terminal tail (CTT) of HIV gp41 remain relatively limited and contradictory. The current study was designed to examine in detail CTT sequence conservation relative to gp120 and the gp41 ectodomain and to examine the conservation of predicted physicochemical and structural properties across a number of divergent HIV clades and groups. Results demonstrate that CTT sequences display intermediate levels of sequence evolution and diversity in comparison to the more diverse gp120 and the more conserved gp41 ectodomain. Despite the relatively high level of CTT sequence variation, the physicochemical properties of the lentivirus lytic peptide domains (LLPs) within the CTT are evidently highly conserved across clades/groups. Additionally, predictions using PEP-FOLD indicate a high level of structural similarity in the LLP regions that was confirmed by circular dichroism measurements of secondary structure of LLP peptides from clades B, C, and group O. Results demonstrate that LLP peptides adopt helical structure in the presence of SDS or trifluoroethanol but are predominantly unstructured in aqueous buffer. Thus, these data for the first time demonstrate strong conservations of characteristic CTT physicochemical and structural properties despite substantial sequence diversity, apparently indicating a delicate balance between evolutionary pressures and the conservation of CTT structure and associated functional roles in virus replication.
authors.affiliation: Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Steckbeck
authors.forename: Jodi K
authors.initials: JK
authors.lastname: Craigo
authors.forename: Christopher O
authors.initials: CO
authors.lastname: Barnes
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Montelaro
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D017124:Conserved Sequence; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000502:physiology*; D015497:HIV-1 / Q000145:classification / Q000502:physiology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D014779:Virus Replication / Q000502:physiology*
chemical_list: D015700:HIV Envelope Protein gp41