Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein Shows an N-Terminal β-Hairpin in the Absence of N-Terminal Proline

Abstract

Feline immunodeficiency virus (FIV) is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS) in cats and wild felines. Its capsid protein (CA) drives the assembly of the viral particle, which is a critical step in the viral replication cycle. Here, the first atomic structure of full-length FIV CA to 1.67 Å resolution is determined. The crystallized protein exhibits an original tetrameric assembly, composed of dimers which are stabilized by an intermolecular disulfide bridge induced by the crystallogenesis conditions. The FIV CA displays a standard α-helical CA topology with two domains, separated by a linker shorter than other retroviral CAs. The β-hairpin motif at its amino terminal end, which interacts with nucleotides in HIV-1, is unusually long in FIV CA. Interestingly, this functional β-motif is formed in this construct in the absence of the conserved N-terminal proline. The FIV CA exhibits a cis Arg–Pro bond in the CypA-binding loop, which is absent in known structures of lentiviral CAs. This structure represents the first tri-dimensional structure of a functional, full-length FIV CA.

Formation of RNA Granule-Derived Capsid Assembly Intermediates Appears To Be Conserved between Human Immunodeficiency Virus Type 1 and the Nonprimate Lentivirus Feline Immunodeficiency Virus

“…The FIV CA-NTD model obtained from SWISS-MODEL and the FIV CA-CTD crystal structure (PDB accession number 5DCK [18]) were separately aligned with HIV-1 CA structure (PDB accession number 5L93 [59]) using FATCAT (91, 92), resulting in optimized root mean square deviations (RMSD) of 2.75 Å for the NTD domains and 1.94 Å for the CTD domains. While this report was in the final stages of review, a structure of the full FIV CA protein was published (PDB accession number 5NA2 [93]). Our RELIK-based model for FIV CA-NTD fits well with the newly published FIV CA model, with alignment of the RELIK-based CA-NTD structure and the newly published FIV CA-NTD structure resulting in an RMSD of 2.67 Å using FATCAT.…”

Properties and Functions of Feline Immunodeficiency Virus Gag Domains in Virion Assembly and Budding

“…The recent determination of the crystal structure of the FIV CA has revealed that the molecule displays the standard α-helical CA topology with two domains separated by a linker [ 77 ] ( Figure 4 ). However, the crystallized FIV CA shows some features that differ from known structures of lentiviral CA proteins [ 78 , 79 ], such as the formation of a β-hairpin motif at its amino terminal end in the absence of a proline residue at position 1 and the presence of a cis Arg89-Pro90 bond [ 77 ]. It has been reported that the FIV CA binds the peptidyl-prolyl cis - trans isomerase cyclophilin A (CypA) [ 80 ].…”

Looking for Novel Capsid Protein Multimerization Inhibitors of Feline Immunodeficiency Virus

“…Moreover, a recent study identified residues of the FIV capsid, which are important for FIV capsid assembly and are located in helix 4. Although our compounds do not bind directly to these two residues, these compounds could change the conformation of this region upon binding, resulting in the inhibition of p24:p24 interactions during capsid assembly [ 39 ].…”

“…The FIV CA protein was expressed and purified mostly as described [ 35 , 39 ]. Escherichia coli cells (BL2I (DE3) pLysS, Lucigen, Middleton, WI, USA) transformed with pRSET-p24EDCP-T were grown in Lysogenic broth medium (Sigma-Aldrich, Saint-Quentin-Fallavier, France), supplemented with 50 mg/mL of ampicillin, at 37 °C.…”