The capsid protein of human immunodeficiency virus: intersubunit interactions during virus assembly

Abstract

The capsid protein (CA) of HIV‐1 is composed of two domains, the N‐terminal domain (NTD) and the C‐terminal domain (CTD). During the assembly of the immature HIV‐1 particle, both CA domains constitute a part of the Gag polyprotein, which forms a spherical capsid comprising up to 5000 radially arranged, extended subunits. Gag–Gag interactions in the immature capsid are mediated in large part by interactions between CA domains, which are involved in the formation of a lattice of connected Gag hexamers. After Gag proteolysis during virus maturation, the CA protein is released, and approximately 1000–1500 free CA subunits self‐assemble into a truncated cone‐shaped capsid. In the mature capsid, NTD–NTD and NTD–CTD interfaces are involved in the formation of CA hexamers, and CTD–CTD interfaces connect neighboring hexamers through homodimerization. The CA–CA interfaces involved in the assembly of the immature capsid and those forming the mature capsid are different, at least in part. CA appears to have evolved an extraordinary conformational plasticity, which allows the creation of multiple CA–CA interfaces and the occurrence of CA conformational switches. This minireview focuses on recent structure–function studies of the diverse CA–CA interactions and interfaces involved in HIV‐1 assembly. Those studies are leading to a better understanding of molecular recognition events during virus morphogenesis, and are also relevant for the development of anti‐HIV drugs that are able to interfere with capsid assembly or disassembly.

Protein intrinsic disorder as a flexible armor and a weapon of HIV-1

“…Therefore, during the HIV-1 morphogenesis, the CA polypeptide is involved in the creation of diverse CA-CA interfaces and other CA-ligand interfaces, thus possessing an extraordinary conformational plasticity [167]. For example, the hexagonal capsid lattice is composed of three different types of interfaces: a six-fold symmetric NTD-NTD interface that creates hexameric rings, an intermolecular interface between the two domains (NTD-CTD) that reinforces the hexamer, and a homodimeric CTD-CTD interface that links the hexameric building blocks into an infinite hexagonal lattice [166].…”

“…Location of the a-helix seen in the crystal structure of the VifElonginB-ElonginC complex is shown by the black bar between the disorder score panels. Gray shaded areas correspond to the NTD domain (residues 1-100) that contains an RNA-binding domain, and discontinuous binding sites for A3G and A3F, and to the SOCS box domain (residues 144-173) containing a BC-box region (residues 144-159) and a putative Cullin box (residues [159][160][161][162][163][164][165][166][167][168][169][170][171][172][173]. Dark blue line shows the location of a predicted a-MoRF to one partner [28,29].…”

Properties and functions of the nucleocapsid protein in virus assembly

“…The core structure or capsid is composed of about 1,500 molecules of capsid (CA) protein p24 in the form of 250 hexamers surrounding the nucleocapsid structure or virus replicative machinery. [11][12][13] The virus nucleocapsid can be viewed as a ribonucleoparticle or RNP, since the major structural components correspond to the unique genomic RNA coated by molecules of nucleocapsid protein NCp7. A unique feature of the genomic RNA is its dimeric 60S form where the two RNA molecules are in close contact via non-covalent interactions involving the 5' DLS-DIS (Dimer-Linkage-Structure and Dimerization Initiation Sequence) sequences as well as many other contact sequences.…”

A Novel Tuberculosis DNA Vaccine in an HIV-1 p24 Protein Backbone Confers Protection against Mycobacterium tuberculosis and Simultaneously Elicits Robust Humoral and Cellular Responses to HIV-1

“…Studies show that HIV-1 p24 can stimulate robust antigen-specific humoral and cellular responses (3,27,41). Therefore, in the pP24-Mtb vaccine, the scaffold protein p24 for incor- poration of M. tuberculosis epitopes was also used as an immunogen to induce an immune response to HIV-1.…”