{"id":13998,"date":"2017-07-03T00:00:17","date_gmt":"2017-07-03T07:00:17","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=13998"},"modified":"2024-01-30T15:32:11","modified_gmt":"2024-01-30T23:32:11","slug":"tilted-microscopy-technique-better-reveals-protein-structures","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/tilted-microscopy-technique-better-reveals-protein-structures\/","title":{"rendered":"T\u00e9cnica de microscop\u00eda inclinada revela mejor las estructuras de prote\u00ednas"},"content":{"rendered":"

LA JOLLA\u2014La manera convencional de colocar muestras de prote\u00ednas bajo un microscopio electr\u00f3nico durante experimentos de criomicroscop\u00eda electr\u00f3nica (criomem) podr\u00eda no ser la mejor opci\u00f3n para obtener la imagen m\u00e1s n\u00edtida de la estructura de una prote\u00edna. En algunos casos, inclinar una l\u00e1mina de prote\u00ednas congeladas \u2014entre 10 y 50 grados\u2014 mientras se encuentra bajo el microscopio, proporciona datos de mayor calidad y podr\u00eda conducir a una mejor comprensi\u00f3n de una variedad de enfermedades, seg\u00fan una nueva investigaci\u00f3n dirigida por un cient\u00edfico de Salk. Dmitry Lyumkis<\/a>.<\/p>\n

\"\"
As\u00ed como mirar latas de sopa desde diferentes \u00e1ngulos te permite ver diferentes formas, observar prote\u00ednas en un \u00e1ngulo revela distintos aspectos de su estructura. <\/p>\n

Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n. <\/p>\n

Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n

\u201cLa gente ha intentado implementar la inclinaci\u00f3n antes, pero ha habido muchos desaf\u00edos\u201d, dice Lyumkis, becario Helmsley-Salk en el Salk Institute y autor principal del nuevo trabajo, publicado el 3 de julio de 2017 en Naturaleza M\u00e9todos<\/em><\/a>. Hemos eliminado muchos de estos problemas con nuestro nuevo enfoque.\u201c<\/p>\n

La crio-EM, o crio-microscop\u00eda electr\u00f3nica, es una forma de microscop\u00eda electr\u00f3nica de transmisi\u00f3n en la que las muestras se enfr\u00edan r\u00e1pidamente a temperaturas bajo cero antes de ser fotografiadas bajo el microscopio. A diferencia de otros m\u00e9todos com\u00fanmente utilizados para determinar la estructura de las prote\u00ednas, la crio-EM permite que las prote\u00ednas permanezcan en sus conformaciones naturales para su obtenci\u00f3n de im\u00e1genes, lo que podr\u00eda revelar nueva informaci\u00f3n sobre las estructuras. La comprensi\u00f3n de las estructuras de las prote\u00ednas es un paso vital para el desarrollo de nuevas terapias para enfermedades., como en el caso del VIH<\/a>.<\/p>\n

Los investigadores han asumido durante mucho tiempo que las prote\u00ednas adoptan conformaciones aleatorias en la rejilla congelada que se prepara para experimentos de criomicroscop\u00eda electr\u00f3nica, lo que significa que al tomar suficientes im\u00e1genes, los investigadores pueden armar una imagen completa en 3D de la(s) forma(s) de la prote\u00edna desde todas las direcciones de imagen. Pero para muchas prote\u00ednas, el enfoque parece no ser suficiente y partes de las estructuras de las prote\u00ednas permanecen ausentes.<\/p>\n

\u201cLos investigadores est\u00e1n empezando a pensar que las prote\u00ednas en una rejilla de criomicroscop\u00eda electr\u00f3nica no adoptan conformaciones aleatorias despu\u00e9s de todo, sino que se adhieren a la parte superior o inferior de la rejilla de la muestra en orientaciones preferidas\u201d, dice Lyumkis. \u201cPor lo tanto, es posible que no estemos obteniendo una imagen completa de las estructuras de las prote\u00ednas. M\u00e1s importante a\u00fan, este comportamiento puede impedir por completo la determinaci\u00f3n de la estructura para muestras de prote\u00ednas seleccionadas\u2019.\u201d<\/p>\n

Para entender el problema, imagina que tratas de observar las sombras de una docena de latas de conservas para determinar su forma, pero solo ves c\u00edrculos porque todas las latas est\u00e1n exactamente verticales. Sin embargo, al hacer que la luz \u2014o el haz de electrones, en el caso de la criomicroscop\u00eda electr\u00f3nica\u2014 incida sobre las muestras en \u00e1ngulo, podr\u00edas ver mejor su forma real.<\/p>\n

Cuando los investigadores han intentado inclinar muestras bajo un microscopio en el pasado, se han visto limitados por una resoluci\u00f3n deficiente: un \u00e1ngulo implica que el haz de electrones debe atravesar una rejilla m\u00e1s gruesa. Las muestras tambi\u00e9n son m\u00e1s propensas a moverse dentro de la rejilla congelada cuando se inclinan, lo que difumina los datos. Y t\u00e9cnicamente, analizar datos de una muestra inclinada tambi\u00e9n es m\u00e1s desafiante, ya que los m\u00e9todos de criomicroscop\u00eda electr\u00f3nica se dise\u00f1aron con la suposici\u00f3n de que la rejilla que conten\u00eda las prote\u00ednas siempre estaba a la misma distancia del microscopio.<\/p>\n

\"Dmitry
Dmitry Lyumkis<\/p>\n

Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<\/p>\n

Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n

Para abordar estos desaf\u00edos, Lyumkis y sus colegas cambiaron los materiales utilizados para crear la rejilla de crio-EM, grabaron pel\u00edculas de sus datos en lugar de im\u00e1genes fijas y desarrollaron nuevos m\u00e9todos computacionales para analizar la informaci\u00f3n.<\/p>\n

Cuando probaron el nuevo enfoque en la prote\u00edna hemaglutinina de la influenza, una prote\u00edna notoriamente dif\u00edcil de caracterizar mediante criomicroscop\u00eda electr\u00f3nica, el equipo descubri\u00f3 que inclinar la muestra proporcion\u00f3 un conjunto de datos m\u00e1s completo. Cuando la muestra de prote\u00edna estaba plana, los algoritmos t\u00edpicos introdujeron falsos positivos en la forma de la prote\u00edna que no estaban respaldados por datos experimentales. Ese no fue el caso cuando se inclin\u00f3.<\/p>\n

\u201cDebido a la geometr\u00eda de la recolecci\u00f3n de datos, cuando inclinamos, llenamos muchos m\u00e1s datos que caracterizan las mol\u00e9culas, lo que nos da una imagen m\u00e1s completa de la forma de la prote\u00edna\u201d, dice Lyumkis.<\/p>\n

Los algoritmos que Lyumkis y su equipo desarrollaron \u2014que incluyen formas de analizar si un experimento de crio-EM est\u00e1 introduciendo datos err\u00f3neos, as\u00ed como m\u00e9todos para interpretar un experimento inclinado\u2014 ahora est\u00e1n disponibles p\u00fablicamente. Esperan que otros investigadores comiencen a usarlos y que se conviertan en una m\u00e9trica est\u00e1ndar para la validaci\u00f3n de estructuras de crio-EM (dado que la mayor\u00eda de las estructuras derivadas experimentalmente sufren de informaci\u00f3n faltante en diferentes grados).<\/p>\n

\u201cUna de las ideas que estamos considerando ahora es si la recopilaci\u00f3n de datos siempre deber\u00eda realizarse con una inclinaci\u00f3n en lugar de la forma convencional\u201d, dice Lyumkis. \u201cNo har\u00e1 da\u00f1o y deber\u00eda ayudar\u201d.\u201d<\/p>\n

Otros investigadores del estudio fueron Yong Zi Tan, Philip Baldwin, Clinton Potter y Bridget Carragher de la Centro de Biolog\u00eda Estructural de Nueva York<\/a>, y Joseph David y James Williamson de El Instituto Scripps de Investigaci\u00f3n<\/a>.<\/p>\n

El trabajo y los investigadores involucrados fueron apoyados por subvenciones de la Agencia de Ciencia, Tecnolog\u00eda e Investigaci\u00f3n Singapur<\/a>, la Fundaci\u00f3n Ben\u00e9fica Leona M. y Harry B. Helmsley<\/a>, los EE. UU. Institutos Nacionales de Salud<\/a>, la Fundaci\u00f3n Jane Coffin Childs<\/a>, la Instituto Nacional de Envejecimiento<\/a>, la Instituto Nacional de Ciencias M\u00e9dicas Generales<\/a> y el Fundaci\u00f3n Simons<\/a>.<\/p>","protected":false},"featured_media":14011,"template":"","faculty":[320],"disease-research":[122,331],"class_list":["post-13998","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-dmitry-lyumkis","disease-research-immune-system-biology","disease-research-protein-interactions"],"acf":[],"yoast_head":"\nTilted microscopy technique better reveals protein structures - 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\/tilted-microscopy-technique-better-reveals-protein-structures\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Tilted microscopy technique better reveals protein structures - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014The conventional way of placing protein samples under an electron microscope during cryo-EM experiments may fall flat when it comes to getting the best picture of a protein\u2019s structure. 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