PMID:23184932

Citation	Chen, K, Piszczek, G, Carter, C and Tjandra, N (2013) The maturational refolding of the β-hairpin motif of equine infectious anemia virus capsid protein extends its helix α1 at capsid assembly locus. J. Biol. Chem. 288:1511-20
Abstract	A retroviral capsid (CA) protein consists of two helical domains, CA(N) and CA(C), which drive hexamer and dimer formations, respectively, to form a capsid lattice. The N-terminal 13 residues of CA refold to a β-hairpin motif upon processing from its precursor polyprotein Gag. The β-hairpin is essential for correct CA assembly but unexpectedly it is not within any CA oligomeric interfaces. To understand the β-hairpin function we studied the full-length CA protein from equine infectious anemia virus (EIAV), a lentivirus sharing the same cone-shaped capsid core as HIV-1. Solution NMR spectroscopy is perfectly suited to study EIAV-CA that dimerizes weaker than HIV-1-CA. Comparison between the wild-type (wt) EIAV-CA and a variant lacking the β-hairpin structure demonstrated that folding of the β-hairpin specifically extended the N terminus of helix α1 from Tyr(20) to Pro(17). This coil to helix transition involves the conserved sequence of Thr(16)-Pro(17)-Arg(18) (Ser(16)-Pro(17)-Arg(18) in HIV-1-CA). The extended region of helix α1 constituted an expanded EIAV-CA(N) oligomeric interface and overlapped with the HIV-1-CA hexamer-core residue Arg(18), helical in structure and pivotal in assembly. Therefore we propose the function of the maturational refolding of the β-hairpin in CA assembly is to extend helix α1 at the N terminus to enhance the CA(N) oligomerization along the capsid assembly core interface. In addition, NMR resonance line broadening indicated the presence of micro-millisecond exchange kinetics due to the EIAV-CA(N) domain oligomerization, independent to the faster EIAV-CA(C) domain dimerization.
Links	PubMed PMC3548464 Online version:10.1074/jbc.M112.425140
Keywords	Amino Acid Sequence; Capsid Proteins/chemistry; Capsid Proteins/genetics; Capsid Proteins/metabolism; Conserved Sequence; Escherichia coli/genetics; Gene Expression; HIV-1/chemistry; HIV-1/genetics; Infectious Anemia Virus, Equine/chemistry; Infectious Anemia Virus, Equine/genetics; Models, Molecular; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Protein Folding; Protein Multimerization; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Structural Homology, Protein; Virion/chemistry; Virion/genetics; Virus Assembly
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