Crystal structure of dimeric HIV-1 capsid protein

Abstract

X-ray diffraction analysis of a human immunodeficiency virus (HIV-1) capsid (CA) protein shows that each monomer within the dimer consists of seven alpha-helices, five of which are arranged in a coiled coil-like structure. Sequence assignments were made for two of the helices, and tentative connectivity of the remainder of the protein was confirmed by the recent solution structure of a monomeric N-terminal fragment. The C-terminal third of the protein is mostly disordered in the crystal. The longest helices in the coiled coil-like structure are separated by a long, highly antigenic peptide that includes the binding site of an antibody fragment complexed with CA in the crystal. The site of binding of the Fab, the position of the antigenic loop and the site of cleavage between the matrix protein and CA establish the side of the dimer that would be on the exterior of the retroviral core.

Thermodynamic Dissection of a Low Affinity Protein-Protein Interface Involved in Human Immunodeficiency Virus Assembly

“…Dimerization of the capsid protein (CA) of HIV-1 through its C-terminal domain (CA-C) is a major driving force in virus morphogenesis and budding from the cell (23)(24)(25)(26). The threedimensional structures of CA from HIV-1 and other retroviruses are known (27)(28)(29)(30)(31)(32)(33)(34). Image reconstruction by cryo-electron microscopy (35) and measurements of amide hydrogen exchange (36) of HIV-1 capsids formed in vitro have provided direct evidence for the relevance in the assembled capsid of the homotypic CA-C interactions determined by x-ray crystallography of the soluble CA-C dimer (29,30).…”

Maturation-induced Conformational Changes of HIV-1 Capsid Protein and Identification of Two High Affinity Sites for Cyclophilins in the C-terminal Domain

“…Model of CyPA action on the capsid cone architecture. The capsid protein p24 of HIV-1 is supposed to dimerize by interactions between the N-terminal domains (N) of two p24 molecules and to oligomerize to higher order structures by aggregation of p24 dimers through their C-terminal domains (C) containing the MHR (20,34). After processing of the Gag polyprotein and due to conformational changes, high affinity binding sites for cyclophilins are generated in the C-terminal domain of p24 additionally to the low affinity Gly-Pro 90 site in the N-terminal domain.…”

Monte Carlo Simulations of HIV Capsid Protein Homodimer

“…The self-assembly of the CA proteins has been extensively studied using X-ray, NMR, and cryo-electron microscopy (Cryo-EM). [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Remarkably, a complete atomic model of the capsid was recently obtained by Cryo-EM combined with all-atom simulations. 17 Other theoretical and computational studies [27][28][29][30] also provided important insight into the structure and the assembling process for the HIV capsid.…”