Nuclear pore passage of the HIV capsid is driven by its unusual surface amino acid composition.

ABSTRACT: Nuclear transport receptors (NTRs) carry cargo across the permeability barrier of nuclear pore complexes (NPCs)-an FG phase condensed from disordered but cohesive FG-repeat domains. This phase repels inert macromolecules but allows NTR passage. When the human immunodeficiency virus (HIV) infects nondividing cells, its capsid is transported into nuclei not like a cargo but crosses NPCs like an NTR. Here we uncovered the molecular determinants of the capsid's NTR behavior. The FG-binding pocket is insufficient. Hexameric and pentameric capsomers contribute. The highly exposed outer capsid surface is key. It lacks FG-repulsive charged residues (K, D and E) that are very abundant on other protein surfaces. FG-attractive residues dominate the capsid surface instead. Introducing FG-repulsive ami

SUBMITTER: Fu L 

PROVIDER: S-EPMC12700808 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature