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Updated: Jul 5, 2025
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Nucleocapsid Annealing-Mediated Electrophoresis NAME Assay Allows the Rapid Identification of HIV-1 Nucleocapsid Inhibitors
Published on: January 19, 2015
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HIV-1 capsid shape, orientation, and entropic elasticity regulate translocation into the nuclear pore complex
1Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, IL 60637.
Summary
HIV-1 capsid nuclear import relies on compatible morphology and orientation for translocation through the nuclear pore complex. Capsid elasticity aids structural integrity during this critical viral life cycle step.
Area of Science:
- Virology
- Structural Biology
- Computational Biology
Background:
- Nuclear import and uncoating are essential for HIV-1 replication, involving capsid translocation through the nuclear pore complex (NPC).
- The mechanism of intact HIV-1 capsid passage through the NPC's central channel requires further elucidation.
Purpose of the Study:
- To investigate the molecular interactions governing HIV-1 capsid translocation through the NPC central channel.
- To understand how capsid morphology, NPC dimensions, and nucleoporin interactions influence translocation dynamics.
Main Methods:
- Development of a "bottom-up" coarse-grained (CG) model of the human NPC using cryo-electron tomography data.
- Construction of composite membrane-embedded CG NPC models to simulate capsid-NPC interactions.
Main Results:
- Successful translocation depends on capsid morphology-channel dimension compatibility and proper capsid orientation.
- Translocation is driven by interactions between phenylalanine-glycine nucleoporins and the capsid.
- Capsid elasticity and internal genomic material contribute to structural integrity and lattice disorder during translocation.
Conclusions:
- HIV-1 capsid translocation through the NPC is a regulated process influenced by physical and molecular factors.
- Intrinsic capsid elasticity is crucial for maintaining structural integrity under the stress of nuclear import.
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