title: A triclinic crystal structure of the carboxy-terminal domain of HIV-1 capsid protein with four molecules in the asymmetric unit reveals a novel packing interface.
abstract: The Gag precursor is the major structural protein of the virion of human immunodeficiency virus-1 (HIV-1). Capsid protein (CA), a cleavage product of Gag, plays an essential role in virus assembly both in Gag-precursor multimerization and in capsid core formation. The carboxy-terminal domain (CTD) of CA contains 20 residues that are highly conserved across retroviruses and constitute the major homology region (MHR). Genetic evidence implies a role for the MHR in interactions between Gag precursors during the assembly of the virus, but the structural basis for this role remains elusive. This paper describes a novel triclinic structure of the HIV-1 CA CTD at 1.6 Å resolution with two canonical dimers of CA CTD in the asymmetric unit. The canonical dimers form a newly identified packing interface where interactions of four conserved MHR residues take place. This is the first structural indication that these MHR residues participate in the putative CTD-CTD interactions. These findings suggest that the molecules forming this novel interface resemble an intermediate structure that participates in the early steps of HIV-1 assembly. This interface may therefore provide a novel target for antiviral drugs.
authors.affiliation: Molecular Microbiology and Biotechnology, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Lampel
authors.forename: Oren
authors.initials: O
authors.lastname: Yaniv
authors.forename: Or
authors.initials: O
authors.lastname: Berger
authors.forename: Eran
authors.initials: E
authors.lastname: Bacharach
authors.forename: Ehud
authors.initials: E
authors.lastname: Gazit
authors.forename: Felix
authors.initials: F
authors.lastname: Frolow
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000737:chemistry* / Q000502:physiology; D003460:Crystallization; D015497:HIV-1 / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D019065:Virus Assembly / Q000502:physiology*
chemical_list: D036022:Capsid Proteins
keywords: Gag precursor; HIV-1; capsid protein