MxB N-Terminus Adopts a Stable α-Helix to Engage the HIV-1 Capsid Trimer Interface

The HIV-1 capsid, made up of CA proteins arranged in a conical shape, plays a crucial role in host-pathogen interactions. Certain host factors, like Myxovirus resistance protein B (MxB), help control HIV-1 infection by recognizing the larger CA lattice instead of individual proteins. MxB binds to the capsid through its N-terminal part, which contains a series of arginine residues (RRR).

This binding prevents HIV-1 infection at the very beginning of the infection. So far, scientists have not understood how MxB interacts with the capsid. In this research, a detailed look at the CA lattice interacting with the MxB N-terminal fragment was done using a technique called cryo-electron tomography and averaging of small pieces of images.

By combining these electron microscope structures with computer simulations, researchers have found specific places where MxB's N-terminal part connects with the CA trimer interfaces. Most importantly, they discovered that residues 10-20 in the MxB N-terminal part make an alpha-helical structure that helps bind the CA trimer interface.

This is a new way for the capsid to be engaged. These discoveries give us a better understanding of how MxB and other cell helpers recognize the capsid and lay the foundation for making new medicines that target the capsid.