Scholarlink

<p>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 amino acids impedes FG phase partitioning, NPC targeting and NPC passage of assembled capsids. Capsids are, thus, made soluble in the FG phase by a myriad of transient FG-attractive interactions originating from individual surface side chains. We propose that CPSF6 releases the capsid from NPCs by masking its FG-attractive surface and switching the capsid to an FG-repulsive species.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月9日

查看全文
  • Liran Fu,
  • Shiya Cheng,
  • Dietmar Riedel,
  • Leonie Kopecny,
  • Melina Schuh,
  • Dirk Görlich

摘要

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 amino acids impedes FG phase partitioning, NPC targeting and NPC passage of assembled capsids. Capsids are, thus, made soluble in the FG phase by a myriad of transient FG-attractive interactions originating from individual surface side chains. We propose that CPSF6 releases the capsid from NPCs by masking its FG-attractive surface and switching the capsid to an FG-repulsive species.