Molecule of the Month: HIV Capsid

Viruses come in many shapes and sizes, ranging from simple protein shells filled with RNA or DNA to membrane-enveloped particles that rival cells in complexity. HIV is one of these complex viruses, surrounded by a membrane and filled with a diverse collection of viral and cellular molecules. The genome of HIV, which is composed of two strands of RNA, is packaged inside a distinctive cone-shaped capsid, which protects the RNA and delivers it to the cells that HIV infects.

The HIV capsid is built from a single protein, called capsid protein, shown here on the left from PDB entry 1e6j . Capsid protein, also known as CA or p24, folds to form two domains connected by a flexible linker. This flexibility gives the protein a lot of options for assembly. The larger domain associates with other copies of the protein to form rings of six, and slightly less often, rings of five. The smaller domain then links these rings together to form the larger structure.

The flexibility allows the formation of structures that aren't as perfectly symmetrical as the capsids of viruses like poliovirus or rhinovirus. Instead, HIV capsid forms an unusual cone-shaped structure, with twelve of the pentameric rings (shown here in orange) and over a hundred hexamers (shown here in red). This model was constructed based on electron micrographs, using PDB entries 3h47 and 2kod and refining the model with molecular dynamics. Two models were obtained that are consistent with the electron microscope images: a model with 216 hexamers (shown here from PDB entry 3j3q ) and a slightly smaller model with 186 hexamers (PDB entry 3j3y ). Because of their large size, these HIV capsid structures are milestone entries for the PDB archive: you can read more about this on the wwPDB news.

TRIM5 is one of the weapons deployed in the ongoing battle being fought between living organisms and viruses. TRIM5 binds to the retroviral capsid and interferes with the uncoating process. At this point in our evolution, the human version of TRIM5 is not effective against HIV, but it blocks other retroviruses. However, the TRIM5 protein from rhesus monkeys, shown here from PDB entry 2lm3 , is highly potent against HIV. Other cellular proteins are used by HIV to assist in viral replication. As HIV is budding from an infected cell, the cellular enzyme cyclophilin A binds to capsid, as shown here from PDB entry 1ak4 . Researchers are still working out its function in the viral lifecycle, but it seems to be essential for the proper uncoating of the virus when it infects a new cell.