bims-nucpor Biomed News
on Nuclear pore complex and nucleoporins in stress, aging and disease
Issue of 2023–10–15
two papers selected by
Sara Mingu, Johannes Gutenberg University
  1. The interplay of nuclear pores and lipids.
  2. Elasticity of the HIV-1 Core Facilitates Nuclear Entry and Infection.
  1. Curr Opin Cell Biol. 2023 Oct 04. pii: S0955-0674(23)00100-X. [Epub ahead of print]85 102251
    The interplay of nuclear pores and lipids.
    Edvinas Stankunas, Alwin Köhler.
      Nuclear pore complexes (NPCs) mediate the bidirectional transport of cargo across the nuclear envelope (NE). NPCs are also membrane remodeling machines with a capacity to curve and fuse the membranes of the NE. However, little is known about the interplay of NPCs and lipids at a mechanistic level. A full understanding of NPC structure and function needs to encompass how the NPC shapes membranes and is itself shaped by lipids. Here we attempt to connect recent findings in NPC research with the broader field of membrane biochemistry to illustrate how an interplay between NPCs and lipids may facilitate the conformational plasticity of NPCs and the generation of a unique pore membrane topology. We highlight the need to better understand the NPC's lipid environment and outline experimental avenues towards that goal.
    DOI:  https://doi.org/10.1016/j.ceb.2023.102251
  2. bioRxiv. 2023 Sep 30. pii: 2023.09.29.560083. [Epub ahead of print]
    Elasticity of the HIV-1 Core Facilitates Nuclear Entry and Infection.
    Akshay Deshpande, Alexander J Bryer, Jonathan Andino, Jiong Shi, Jun Hong, Cameron Torres, Shimon Harel, Ashwanth C Francis, Juan R Perilla, Christopher Aiken, Itay Rousso.
      HIV-1 infection requires passage of the viral core through the nuclear pore of the cell, a process that depends on functions of the viral capsid 1,2 . Recent studies have shown that HIV- 1 cores enter the nucleus prior to capsid disassembly 3-5 . Interactions with the nuclear pore complex are necessary but not sufficient for nuclear entry, and the mechanism by which the viral core traverses the comparably sized nuclear pore is unknown. Here we show that the HIV-1 core is highly elastic and that this property is linked to nuclear entry and infectivity. Using atomic force microscopy-based approaches, we found that purified wild type cores rapidly returned to their normal conical morphology following a severe compression. Results from independently performed molecular dynamic simulations of the mature HIV-1 capsid also revealed its elastic property. Analysis of four HIV-1 capsid mutants that exhibit impaired nuclear entry revealed that the mutant viral cores are brittle. Suppressors of the mutants restored elasticity and rescued infectivity and nuclear entry. Elasticity was also reduced by treatment of cores with the capsid-targeting compound PF74 and the antiviral drug lenacapavir. Our results indicate that capsid elasticity is a fundamental property of the HIV-1 core that enables its passage through the nuclear pore complex, thereby facilitating infection. These results provide new insights into the mechanisms of HIV-1 nuclear entry and the antiviral mechanisms of HIV-1 capsid inhibitors.
    DOI:  https://doi.org/10.1101/2023.09.29.560083
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