Name: mapping protein interaction networks
Uploaded: 2023-04-30T18:28:44.000Z
Duration: 2 min 26 s
Channel: JoVE

K12 Standards

Next Generation Science Standards

High School

Life Science

from-molecules-to-organisms-structures-and-processes

From Molecules to Organisms: Structures and Processes

HS-LS1-1

Protein Networks

Un solo organismo puede contener miles de proteínas diferentes, y la mayoría de estas proteínas deben interactuar con otras proteínas para realizar sus funciones.
Muchas proteínas tienen múltiples socios de unión, lo que da lugar a una compleja red de interacciones proteicas.
Varias técnicas de laboratorio, incluidos los métodos bioquímicos y computacionales, ayudan a los científicos a comprender estas redes de proteínas.
El marcaje de afinidad es un método que se utiliza a menudo para aislar una proteína junto con cualquier otra molécula que interactúe. Una etiqueta de afinidad es un motivo de aminoácido que se añade genéticamente a la proteína de interés. Esta etiqueta se puede utilizar para aislar la proteína objetivo junto con otras proteínas asociadas a ella. 
Las proteínas que interactúan con la proteína marcada se pueden analizar para determinar su identidad y nuevas interacciones.
Un método para analizar estas interacciones de proteínas desconocidas es dividir las proteínas en segmentos cortos y analizarlas con un espectrómetro de masas para determinar las secuencias de aminoácidos. Estas secuencias se pueden comparar con las bases de datos de secuencias de proteínas existentes para identificar proteínas asociadas desconocidas. 
Además, las bases de datos de libre acceso, como IntAct, tienen datos de interacción proteína-proteína cargados por investigadores de todo el mundo disponibles para su comparación. Otras bases de datos, junto con un número creciente de herramientas bioinformáticas avanzadas, se pueden utilizar para predecir las interacciones moleculares de una proteína desconocida
Los mapas de redes de interacción proteína-proteína se utilizan para visualizar estas interacciones entre las proteínas de una célula. Los círculos son nodos, que representan una proteína en particular, y las líneas son bordes, que conectan una proteína con las otras proteínas que interactúan. 
El examen de los mapas de interacción de las proteínas puede ayudar a predecir las funciones de las proteínas. Si el patrón de interacción de los bordes de conexión de una proteína desconocida es similar al de otro nodo, estos dos nodos pueden actuar de manera similar.
Algunos nodos aparecerán como centros altamente conectados, cuyo estudio puede conducir al descubrimiento de mecanismos fundamentales para mantener la salud de la célula, ayudando así en el desarrollo de fármacos.

<ol>
	<li>Alberts et al., 6ª edición; páginas 166-169</li>
	<li>Morris, J. H., Knudsen, G. M., Verschueren, E., Johnson, J. R., Cimermancic, P., Greninger, A. L., & Pico, A. R. (2014). Purificación por afinidad-espectrometría de masas y análisis de redes para comprender las interacciones proteína-proteína. Protocolos de la naturaleza, 9(11), 2539.</li>
	<li>Ottman, C. (2013). Interacciones proteína-proteína: una visión general. Interacciones proteína-proteína en el descubrimiento de fármacos.</li>
	<li>Jordán, F., Nguyen, T. P., & Liu, W. C. (2012). Estudio de las redes de interacción proteína-proteína: una visión sistémica de las enfermedades. Sesiones informativas sobre genómica funcional, 11(6), 497-504.</li>
	<li>Berggård, T., Linse, S., & James, P. (2007). Métodos para la detección y análisis de interacciones proteína-proteína. Proteómica, 7(16), 2833-2842.</li>
	<li>Gingras, A. C., Gstaiger, M., Raught, B., & Aebersold, R. (2007). Análisis de complejos proteicos mediante espectrometría de masas. Nature reviews Biología celular molecular, 8(8), 645.</li>
</ol>

redes de proteínas

Un organismo puede tener miles de proteínas diferentes y estas proteínas deben cooperar para garantizar la salud de un organismo. Las proteínas se unen a otras proteínas y forman complejos para llevar a cabo sus funciones. Muchas proteínas interactúan con muchas otras proteínas creando una red compleja de interacciones proteicas.

Estas interacciones se pueden representar a través de mapas que representan redes de interacción proteína-proteína, representadas como nodos y bordes. Los nodos son círculos representativos de una proteína y los bordes son líneas que conectan dos proteínas que interactúan. Estas redes proporcionan una manera de visualizar la complejidad de las interacciones proteína-proteína en un sistema. Estos mapas pueden incluir tanto interacciones estables, como las que se forman en complejos proteicos, como interacciones transitorias. Las interacciones de proteínas que ocurren en una célula, un organismo o un contexto biológico específico pueden denominarse colectivamente "interactoma".

Las redes de proteínas se pueden estudiar utilizando diversos métodos bioquímicos y computacionales. Uno de los primeros pasos en el estudio de las interacciones entre proteínas es aislar una proteína de interés junto con las demás proteínas asociadas. Esto se puede llevar a cabo marcando la proteína de interés con una etiqueta de afinidad, como una etiqueta de histidina. Esta etiqueta luego se puede usar para separar la proteína junto con las otras proteínas mediante cromatografía de afinidad. Luego, las proteínas aisladas se digieren con una proteasa, como la tripsina, y luego se analizan mediante cromatografía líquida-espectrometría de masas (LC-MS). Luego, la masa peptídica se puede comparar con una base de datos con secuencias de proteínas conocidas para determinar su identidad.

Computacionalmente, las interacciones proteína-proteína se pueden analizar utilizando bases de datos y herramientas de predicción. Existen varias bases de datos, como IntAct gestionada por EMBL-EBI, que consisten en interacciones de proteínas predichas y validadas experimentalmente. Se pueden utilizar otras herramientas como STRING del Instituto Suizo de Bioinformática para predecir estas redes de interacción.

El estudio de las redes de proteínas puede conducir a descubrimientos científicos, como determinar la función de una proteína desconocida. Examinar los cambios en estas redes puede ayudar a dilucidar las diferencias entre células sanas y enfermas. Esta información también se puede utilizar para aplicaciones cruciales, como el diseño de fármacos para el tratamiento de enfermedades. El análisis de redes de proteínas puede identificar nodos altamente conectados que pueden ser cruciales para la supervivencia celular, que pueden atacar el cáncer y enfermedades en las que se desea la muerte celular, pero que no serían adecuados para la mayoría de las enfermedades. Por otro lado, los nodos menos conectados que sólo interactúan con unas pocas vías específicas pueden ser atacados si una función celular específica se ve afectada, y el diseño de fármacos que interactúen con estos nodos menos conectados puede provocar menos efectos secundarios.

Redes de proteínas

Un organismo puede tener miles de proteínas diferentes, y estas proteínas deben cooperar para garantizar la salud de un organismo. Las proteínas se unen a otras ...

Education

Educación

JoVE Core

Cell Biology

Biología Celular

Unit 1

Unidad 1

Protein Function

Función proteica

KEY TERMS AND CONCEPTS

TÉRMINOS Y CONCEPTOS CLAVE

mapping protein interaction networks

Protein interaction networks show how proteins work together inside a cell. These networks help scientists see which proteins connect with each other and how those links support cell activity.

Researchers often use online tools to build and study these networks. The transcript points to IntAct and STRING as examples of resources that can help predict and organize protein interactions. These tools make it easier to compare protein links and look for patterns in the network.

Protein networks are useful for understanding biological function. They can also help students see that proteins do not act alone. Instead, many proteins form connected systems that support specific cell processes.

Mapping Protein Interaction Networks

ligand binding sites

Ligand Binding Sites in Proteins

Ligand binding sites are specific parts of a protein where a ligand can attach. A ligand is a molecule that binds to another molecule, often to help start or change a biological process. These sites matter because the shape and chemistry of the protein help determine which ligands can fit and bind. Proteins do not bind every ligand in the same way. The binding site provides a matching surface that supports a close interaction. In many cases, this interaction is important for how cells respond...

protein-protein interfaces

Protein Binding Surfaces and Contacts

Protein binding surfaces and contacts help proteins recognize and attach to each other. These interfaces are the regions where two proteins meet and interact. They are important for many cell processes and for how proteins work together. A protein-protein interface is not just a random touch point. It is shaped by the three-dimensional form of each protein. The matching surfaces allow a stable interaction to form when the proteins fit together well. Studying these interfaces helps explain how...

conserved binding sites

Conserved Binding Sites in Protein Families

Conserved binding sites are regions on proteins that stay similar across related proteins. These shared areas often help proteins interact with the same molecules. For this reason, they are useful clues when comparing protein families. A conserved site can help identify where a protein binds. It can also show which parts of the protein are important for function. When the same pattern appears in several proteins, it suggests that the site has been kept through evolution. Scientists look at...

cofactors and coenzymes

Enzyme Helpers: Metals and Vitamins

Enzyme helpers include cofactors and coenzymes. Enzymes are proteins made of amino acids, and the functional groups on those amino acids can drive many chemical reactions through ionic interactions or acid-base reactions. But amino acids alone cannot handle oxidation-reduction and group transfer reactions, so they need non-protein helpers called cofactors. Cofactors are often described as the chemical teeth of an enzyme. They can be metal ions or organic molecules called coenzymes. These...

cooperative allosteric transitions

Allosteric Changes in Protein Shape

Allosteric changes in protein shape help explain how some proteins switch between active and inactive states. These transitions are cooperative, which means a change in one part of the protein can affect other parts of the same molecule. The video focuses on how these shifts in shape support protein function. It also shows that allosteric transitions can be described with different models. In the concerted model, the protein changes shape as a whole. In the sequential model, the change happens...

protein kinases and phosphatases

Protein Kinases and Phosphatases in Cell Control

Protein kinases and phosphatases help control how proteins work in cells. Kinases add phosphate groups to proteins. Phosphatases remove those phosphate groups. This phosphorylation and dephosphorylation process can change a protein’s shape and activity. It is one way cells turn protein function on or off at the right time. These changes also help cells respond to signals and manage many cell activities. Together, protein kinases and phosphatases keep cellular signaling balanced. When one adds...

gtpases and their regulation

GTPase Molecular Switches and Control

GTPases are molecular switches that help control cell activity. They bind guanosine triphosphate, or GTP, and can change between active and inactive states. This switch-like behavior makes them important in many cell processes. The protein is active when GTP is bound and inactive when guanosine diphosphate, or GDP, is bound. GTPases can also turn themselves off by breaking down GTP into GDP. This built-in control helps cells regulate when the protein is on or off. Their activity is regulated...

covalently linked protein regulators

Protein Regulation by Covalent Bonds

Protein regulation by covalent bonds helps control how cells respond to changing conditions. A covalent bond is a strong chemical link, and in this context it can change how a protein behaves. Some regulators work by attaching a chemical group directly to a protein. This covalent change can alter the protein's activity, its location in the cell, or how long it stays active. Because the change is built into the protein itself, it can have a strong effect on cell function. Covalently linked...

protein complexes with interchangeable parts

protein-complexes-with-interchangeable-parts

Modular Protein Complexes in Cells

Protein complexes in cells can be built from interchangeable parts. This modular design lets some complexes share common subunits while still changing their behavior. A well-known example is the ubiquitin ligase complex called SCF. SCF stands for Skp1-Cullin-F-box, and it helps attach ubiquitin, a small protein tag, to target proteins. The core of SCF stays the same, but the F-box protein can change. The interchangeable F-box subunit gives the complex its specificity. Different F-box proteins...

mechanical protein function

Proteins That Generate Cell Movement

Mechanical proteins help cells and tissues move. They turn chemical energy into force and motion. This process is important in many biological systems. These proteins are also called motor proteins. They interact with cell structures and can produce directed movement. In muscle cells, they support contraction. In other cells, they help with transport and shape changes. Mechanical protein function is a key part of how living systems work. It links protein activity to movement at the cellular...

structural protein function

Structural Proteins in Cells and Tissues

Structural proteins help cells and tissues keep their shape and strength. They are an important part of living systems because they provide support where it is needed most. Many structural proteins form fibers or other sturdy forms that resist stretching and wear. These proteins work as building materials in the body and help keep structures stable over time. Examples of structural proteins include collagen, actin, myosin, and keratin. Each one supports a different part of the body, but all...

protein networks

Protein interaction networks show how proteins work together inside a cell. These networks help scientists see which proteins connect with each other and how those links support cell activity. Researchers often use online tools to build and study these networks. The transcript points to IntAct and STRING as examples of resources that can help predict and organize protein interactions. These tools make it easier to compare protein links and look for patterns in the network. Protein networks...

key terms and concepts

Learn how protein interaction networks reveal links between proteins in cells, and how tools like IntAct and STRING help predict and study those connections.

Mapping Protein Interaction Networks | JoVE K12

cell biology

JoVE Core Biología Celular ilustra procesos celulares complejos mediante completos vídeos animados fáciles de entender. Esta colección se centra en los componentes esenciales de las células y su funcionamiento, incluyendo los orgánulos y las membranas, el transporte celular y el metabolismo energético celular. Todo este material se complementa con los vídeos de científicos en acción, que muestran la aplicación de la biología celular en experimentos reales de investigación.

Characteristics of Life

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Covalently Linked Protein Regulators

Protein Complexes with Interchangeable Parts

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Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins, which carry out the essential functions of life through systems of specialized cells. [Assessment Boundary: Assessment does not include identification of specific cell or tissue types, whole body systems, specific protein structures and functions, or the biochemistry of protein synthesis.]

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Blood Withdrawal II

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Overview

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Develop and use a model to illustrate the hierarchical organization of interacting systems that provide specific functions within multicellular organisms. [Clarification Statement: Emphasis is on functions at the organism system level such as nutrient uptake, water delivery, and organism movement in response to neural stimuli. An example of an interacting system could be an artery depending on the proper function of elastic tissue and smooth muscle to regulate and deliver the proper amount of blood within the circulatory system.] [Assessment Boundary: Assessment does not include interactions and functions at the molecular or chemical reaction level.]

HS-LS1-2

What is Homeostasis?

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Negative and Positive Feedback

Homeostatic Imbalance

Homeostasis is the maintenance of a stable internal environment within the body, which is crucial for the proper functioning of cells, tissues, organs, ...

Plan and conduct an investigation to provide evidence that feedback mechanisms maintain homeostasis. [Clarification Statement: Examples of investigations could include heart rate response to exercise, stomate response to moisture and temperature, and root development in response to water levels.] [Assessment Boundary: Assessment does not include the cellular processes involved in the feedback mechanism.]

HS-LS1-3

Mapping Protein Interaction Networks

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