{"id":35176,"date":"2022-07-06T00:00:17","date_gmt":"2022-07-06T07:00:17","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=35176"},"modified":"2024-01-30T14:23:51","modified_gmt":"2024-01-30T22:23:51","slug":"imaging-solves-mystery-of-how-large-hiv-protein-functions-to-form-infectious-virus","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/imaging-solves-mystery-of-how-large-hiv-protein-functions-to-form-infectious-virus\/","title":{"rendered":"Las im\u00e1genes desvelan el misterio de c\u00f3mo funciona una gran prote\u00edna del VIH para formar un virus infeccioso"},"content":{"rendered":"

LA JOLLA\u2014Comprender c\u00f3mo el VIH se replica dentro de las c\u00e9lulas es clave para desarrollar nuevas terapias que podr\u00edan ayudar a casi 40 millones de personas que viven con el VIH en todo el mundo. Ahora, un equipo de cient\u00edficos del Instituto Salk y la Universidad de Rutgers ha determinado por primera vez la estructura molecular del Pol del VIH, una prote\u00edna que desempe\u00f1a un papel clave en las etapas tard\u00edas de la replicaci\u00f3n del VIH, o el proceso a trav\u00e9s del cual el virus se propaga y se disemina por el cuerpo. Es importante destacar que determinar la estructura de la mol\u00e9cula ayuda a responder preguntas de larga data sobre c\u00f3mo la prote\u00edna se descompone para avanzar en el proceso de replicaci\u00f3n. El descubrimiento, publicado en Science Advances<\/em><\/a> el 6 de julio de 2022, revela una nueva vulnerabilidad en el virus que podr\u00eda ser atacada con medicamentos.<\/p>\n

\"Cartoon
Representaci\u00f3n caricaturesca de la estructura de la Pol del VIH-1.
Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.
Cr\u00e9dito: Francesc Xavier Ruiz del Centro de Biotecnolog\u00eda y Medicina Avanzadas de Rutgers<\/figcaption><\/figure>\n

\u201cLa estructura informa la funci\u00f3n y las ideas que obtuvimos al visualizar la arquitectura molecular de Pol nos brindan una nueva comprensi\u00f3n del mecanismo por el cual el VIH se replica\u201d, dice el coautor principal. Dmitry Lyumkis<\/a>, profesor asistente en el Laboratorio de Gen\u00e9tica y Silla de Desarrollo de la Fundaci\u00f3n Hearst en Salk.<\/p>\n

Los cient\u00edficos sab\u00edan previamente que el Pol del VIH, una poliprote\u00edna, se descompone en tres enzimas \u2013una proteasa, una transcriptasa inversa y una integrasa\u2013 que trabajan juntas para ensamblar la forma madura del virus. La proteasa desempe\u00f1a un papel fundamental al iniciar este proceso al fragmentar la mol\u00e9cula para separar los otros componentes. Sin embargo, hasta ahora se desconoc\u00eda c\u00f3mo la proteasa se liberaba a s\u00ed misma, primero de la poliprote\u00edna m\u00e1s grande Gag-Pol del VIH y luego del Pol del VIH, para llevar a cabo esta tarea. El nuevo art\u00edculo sugiere que la proteasa inicia el proceso auto-cort\u00e1ndose o cort\u00e1ndose para liberarse del resto de la mol\u00e9cula, con la ayuda de la transcriptasa inversa y, posiblemente, la integrasa.<\/p>\n

\u201cSe sab\u00eda (pero no se comprend\u00eda) que existe un acoplamiento entre estas enzimas antes de que el Pol del VIH se descomponga. La visualizaci\u00f3n de la estructura del Pol del VIH explica la base de este complejo mecanismo\u201d, afirma Eddy Arnold, coautor principal, profesor de la junta de gobernadores y profesor distinguido en el Centro de Biotecnolog\u00eda Avanzada y Medicina de la Universidad de Rutgers.<\/p>\n

\u201cEl primer desaf\u00edo fue producir una versi\u00f3n estable del VIH Pol para que la estructura pudiera ser analizada, lo que nunca antes se hab\u00eda informado\u201d, dice Jerry Joe Harrison, coautor principal y profesor titular de la Universidad de Ghana.<\/p>\n

\"From
De izquierda a derecha: Dario Passos y Dmitry Lyumkis.
Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.
Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n

\u201cEsta era una pieza clave que faltaba en el rompecabezas estructural del VIH\u201d, a\u00f1ade Arnold.<\/p>\n

El equipo utiliz\u00f3 microscop\u00eda electr\u00f3nica criog\u00e9nica, una t\u00e9cnica de imagen a la que Lyumkis ha hecho importantes contribuciones, para revelar la estructura tridimensional de la mol\u00e9cula de prote\u00edna pol del VIH. Esto llev\u00f3 al descubrimiento de que Pol es un d\u00edmero, lo que significa que est\u00e1 formado por dos prote\u00ednas unidas. El hallazgo fue una sorpresa porque otras prote\u00ednas virales similares son ensamblajes de una sola prote\u00edna.<\/p>\n

El grupo demostr\u00f3 que en esta estructura de dos caras, el componente proteasa de Pol est\u00e1 \u201cligeramente unido\u201d al componente transcriptasa inversa en una configuraci\u00f3n de uni\u00f3n que mantiene la proteasa ligeramente flexible.<\/p>\n

\u201cMantiene a la proteasa a distancia, de forma laxa, y creemos que esto le da a la proteasa un poco de movimiento, lo que a su vez le permite iniciar el corte de poliprote\u00ednas, un requisito previo para la maduraci\u00f3n viral\u201d, dice el co-primer autor Dario Passos, un exinvestigador del laboratorio de Lyumkis en Salk. \u2019Los tratamientos actuales contra el VIH incluyen m\u00faltiples clases de inhibidores para las tres enzimas, y el descubrimiento tambi\u00e9n revela una nueva vulnerabilidad que podr\u00eda ser atacada con medicamentos\u201c.\u201d<\/p>\n

Los autores dicen que el descubrimiento abre la puerta a importante investigaci\u00f3n de seguimiento, incluidos estudios sobre la estructura de la poliprote\u00edna Gag-Pol, m\u00e1s grande y compleja, tambi\u00e9n involucrada en el ensamblaje viral, as\u00ed como a examinar m\u00e1s de cerca el papel de la integrasa en el ensamblaje de la forma madura del virus VIH durante la replicaci\u00f3n.<\/p>\n

Otros autores incluyeron a Jessica F. Bruhn del Salk; Joseph Bauman, Lynda Tuberty y Francesc Xavier Ruiz de Rutgers; y Jeffrey DeStefano de la Universidad de Maryland.<\/p>\n

El trabajo fue financiado por los Institutos Nacionales de Salud, el Instituto Internacional de Educaci\u00f3n, el programa Fulbright, la Fundaci\u00f3n Margaret T. Morris y las Fundaciones Hearst.<\/p>","protected":false},"featured_media":35184,"template":"","faculty":[320],"disease-research":[449,457,122,366,331],"class_list":["post-35176","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-dmitry-lyumkis","disease-research-biochemistry-and-biophysics","disease-research-hiv","disease-research-immune-system-biology","disease-research-infectious-disease","disease-research-protein-interactions"],"acf":[],"yoast_head":"\nImaging solves mystery of how large HIV protein functions to form infectious virus - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/imaging-solves-mystery-of-how-large-hiv-protein-functions-to-form-infectious-virus\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Imaging solves mystery of how large HIV protein functions to form infectious virus - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Understanding how HIV replicates within cells is key for developing new therapies that could help nearly 40 million people living with HIV globally. 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DeStefano, Francesc Xavier Ruiz, Dmitry Lyumkis, Eddy Arnold","doi":"10.1126\/sciadv.abn9874","paper_title":"Cryo-EM Structure of the HIV-1 Pol Polyprotein Provides Insights into Virion Maturation","subhead":"Detailed views of the HIV protein may lead to novel treatments against the virus","home_photo":"","listing_photo":"","legacy_boilerplate":[],"hide_boilerplate":[],"disable_date":false,"listing_excerpt":"","descriptive_blurb":"","has_journal_cover":false,"og_image_override":false,"gallery":false},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure\/35176","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":8,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure\/35176\/revisions"}],"predecessor-version":[{"id":35232,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure\/35176\/revisions\/35232"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/media\/35184"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/media?parent=35176"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/faculty?post=35176"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disease-research?post=35176"}],"curies":[{"name":"la hora de","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}