Structural basis for alternative self-assembly pathways leading to different human immunodeficiency virus capsid-like nanoparticles

The mechanisms that underlie the spontaneous and faithful assembly of virus particles are guiding the design of self-assembling protein-based nanostructures for biomedical or nanotechnological uses. In this study, the human immunodeficiency virus (HIV-1) capsid was used as a model to investigate wha...

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Autores: Escrig Traver, Judith, Marcos Alcalde, Iñigo, Domínguez Zotes, Santos, Abia, David, Gómez Puertas, Paulino, Valbuena Jiménez, Alejandro, García Mateu, Mauricio
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/715937
Acceso en línea:http://hdl.handle.net/10486/715937
https://dx.doi.org/10.1021/acsnano.4c07948
Access Level:acceso abierto
Palabra clave:Architecture
assembly pathways
molecular dynamics
mutational analysis
nanoparticle
self-assembly
virus capsid
Biología y Biomedicina / Biología
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spelling Structural basis for alternative self-assembly pathways leading to different human immunodeficiency virus capsid-like nanoparticlesEscrig Traver, JudithMarcos Alcalde, IñigoDomínguez Zotes, SantosAbia, DavidGómez Puertas, PaulinoValbuena Jiménez, AlejandroGarcía Mateu, MauricioArchitectureassembly pathwaysmolecular dynamicsmutational analysisnanoparticleself-assemblyvirus capsidBiología y Biomedicina / BiologíaThe mechanisms that underlie the spontaneous and faithful assembly of virus particles are guiding the design of self-assembling protein-based nanostructures for biomedical or nanotechnological uses. In this study, the human immunodeficiency virus (HIV-1) capsid was used as a model to investigate what molecular feature(s) may determine whether a protein nanoparticle with the intended architecture, instead of an aberrant particle, will be self-assembled in vitro. Attempts of using the HIV-1 capsid protein CA for achieving in vitro the self-assembly of cone-shaped nanoparticles that contain CA hexamers and pentamers, similar to authentic viral capsids, had typically yielded hexamer-only tubular particles. We hypothesized that a reduction in the stability of a transient major assembly intermediate, a trimer of CA dimers (ToD), will increase the propensity of CA to assemble in vitro into cone-shaped particles instead of tubes. Certain amino acid substitutions at CA-CA interfaces strongly favored in vitro the assembly of cone-shaped nanoparticles that resembled authentic HIV-1 capsids. All-atom MD simulations indicated that ToDs formed by CA mutants with increased propensity for assembly into cone-shaped particles are destabilized relative to ToDs formed by wt CA or by another mutant that assembles into tubes. The results also indicated that ToD destabilization is mediated by conformational distortion of different CA-CA interfaces, which removes some interprotein interactions within the ToD. A model is proposed to rationalize the linkage between reduced ToD stability and increased propensity for the formation of CA pentamers during particle growth in vitro, favoring the assembly of cone-shaped HIV-1 capsid-like nanoparticlesThis work was funded by grants to M.G.M. (MICINN/FEDER EU RTI2018-096635-B-I00 and PID2021-126973OB-I00) and to P.G.-P (MCIU-AEI RTI2018-094434-B-I00 and MICINN FEDER EU PID2021-126625OB-I00/10.13039/501100011033/), and benefitted also from institutional grants from the Severo Ochoa Program for Centers of Excellence in R&D (CEX2021-00154-S) and Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa. M.G.M. is an associate member of the Institute for Biocomputation and Physics of Complex Systems, Zaragoza, Spain.American Chemical SocietyFacultad de Ciencias20242024-10-08research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/mswordhttp://hdl.handle.net/10486/715937https://dx.doi.org/10.1021/acsnano.4c07948reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7159372026-06-23T12:46:27Z
dc.title.none.fl_str_mv Structural basis for alternative self-assembly pathways leading to different human immunodeficiency virus capsid-like nanoparticles
title Structural basis for alternative self-assembly pathways leading to different human immunodeficiency virus capsid-like nanoparticles
spellingShingle Structural basis for alternative self-assembly pathways leading to different human immunodeficiency virus capsid-like nanoparticles
Escrig Traver, Judith
Architecture
assembly pathways
molecular dynamics
mutational analysis
nanoparticle
self-assembly
virus capsid
Biología y Biomedicina / Biología
title_short Structural basis for alternative self-assembly pathways leading to different human immunodeficiency virus capsid-like nanoparticles
title_full Structural basis for alternative self-assembly pathways leading to different human immunodeficiency virus capsid-like nanoparticles
title_fullStr Structural basis for alternative self-assembly pathways leading to different human immunodeficiency virus capsid-like nanoparticles
title_full_unstemmed Structural basis for alternative self-assembly pathways leading to different human immunodeficiency virus capsid-like nanoparticles
title_sort Structural basis for alternative self-assembly pathways leading to different human immunodeficiency virus capsid-like nanoparticles
dc.creator.none.fl_str_mv Escrig Traver, Judith
Marcos Alcalde, Iñigo
Domínguez Zotes, Santos
Abia, David
Gómez Puertas, Paulino
Valbuena Jiménez, Alejandro
García Mateu, Mauricio
author Escrig Traver, Judith
author_facet Escrig Traver, Judith
Marcos Alcalde, Iñigo
Domínguez Zotes, Santos
Abia, David
Gómez Puertas, Paulino
Valbuena Jiménez, Alejandro
García Mateu, Mauricio
author_role author
author2 Marcos Alcalde, Iñigo
Domínguez Zotes, Santos
Abia, David
Gómez Puertas, Paulino
Valbuena Jiménez, Alejandro
García Mateu, Mauricio
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Facultad de Ciencias
dc.subject.none.fl_str_mv Architecture
assembly pathways
molecular dynamics
mutational analysis
nanoparticle
self-assembly
virus capsid
Biología y Biomedicina / Biología
topic Architecture
assembly pathways
molecular dynamics
mutational analysis
nanoparticle
self-assembly
virus capsid
Biología y Biomedicina / Biología
description The mechanisms that underlie the spontaneous and faithful assembly of virus particles are guiding the design of self-assembling protein-based nanostructures for biomedical or nanotechnological uses. In this study, the human immunodeficiency virus (HIV-1) capsid was used as a model to investigate what molecular feature(s) may determine whether a protein nanoparticle with the intended architecture, instead of an aberrant particle, will be self-assembled in vitro. Attempts of using the HIV-1 capsid protein CA for achieving in vitro the self-assembly of cone-shaped nanoparticles that contain CA hexamers and pentamers, similar to authentic viral capsids, had typically yielded hexamer-only tubular particles. We hypothesized that a reduction in the stability of a transient major assembly intermediate, a trimer of CA dimers (ToD), will increase the propensity of CA to assemble in vitro into cone-shaped particles instead of tubes. Certain amino acid substitutions at CA-CA interfaces strongly favored in vitro the assembly of cone-shaped nanoparticles that resembled authentic HIV-1 capsids. All-atom MD simulations indicated that ToDs formed by CA mutants with increased propensity for assembly into cone-shaped particles are destabilized relative to ToDs formed by wt CA or by another mutant that assembles into tubes. The results also indicated that ToD destabilization is mediated by conformational distortion of different CA-CA interfaces, which removes some interprotein interactions within the ToD. A model is proposed to rationalize the linkage between reduced ToD stability and increased propensity for the formation of CA pentamers during particle growth in vitro, favoring the assembly of cone-shaped HIV-1 capsid-like nanoparticles
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-10-08
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/715937
https://dx.doi.org/10.1021/acsnano.4c07948
url http://hdl.handle.net/10486/715937
https://dx.doi.org/10.1021/acsnano.4c07948
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/msword
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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