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 seul organisme peut contenir des milliers de protéines différentes. Et la plupart de ces protéines doivent interagir avec d'autres protéines afin d'exercer leurs fonctions. De nombreuses protéines ont plusieurs partenaires de liaison qui se traduit par un réseau complexe d'interactions protéiques.Diverses techniques de laboratoire, y compris les méthodes biochimiques et les méthodes de calcul, aident les scientifiques à comprendre ces réseaux de protéines. Le marquage par affinité est une méthode souvent utilisée pour isoler une protéine de toute autre molécule en interaction. Un tag d'affinité est un motif d'acides aminés qui est génétiquement ajouté à la protéine d'intérêt.Ce tag peut être utilisé pour isoler la protéine cible des autres protéines qui lui sont associées. Les protéines qui interagissent avec la protéine marquée peuvent être analysées afin de déterminer leur identité et de nouvelles interactions. Une méthode d'analyse de ces interactions de protéines inconnues est de diviser les protéines en segments courts et des les analyser à l'aide d'un spectromètre de masse pour déterminer les séquences d'acides aminés.Ces séquences peuvent être a comparé à des bases de données de séquences de protéines existantes pour identifier des protéines associées inconnues. En outre, les bases de données disponibles gratuitement, telles que IntAct, disposent de données sur l'interaction protéine-protéine téléchargées par des chercheurs du monde entier et disponibles pour faire des comparaisons. D'autres bases de données, associées à un nombre croissant d'outils de bioinformatique de pointe, peuvent être utilisées pour prédire les interactions moléculaires d'une protéine inconnue.Les cartes du réseau d'interaction protéine-protéine sont utilisées pour visualiser ces interactions entre les protéines dans une cellule. Les cercles sont des nœuds qui représentent une protéine particulière. Et les lignes sont des arêtes qui relient une protéine aux autres protéines en interaction.L'examen des cartes d'interaction des protéines peut aider à prédire les fonctions protéiques. Si le modèle d'interaction des arêtes de connexion d'une protéine inconnue est similaire à celui d'un autre nœud, ces deux nœuds peuvent agir de la même manière. Certains nœuds apparaîtront comme des hubs hautement connectés, dont l'étude peut mener à la découverte de mécanismes fondamentaux pour maintenir en bonne santé la cellule, ce qui facilite le développement de médicaments.

<ol>
	<li>Alberts et al., 6e édition ; pages 166-169</li>
	<li>Morris, J. H., Knudsen, G. M., Verschueren, E., Johnson, J. R., Cimermancic, P., Greninger, A. L. et Pico, A. R. (2014). Purification d’affinité-spectrométrie de masse et analyse de réseau pour comprendre les interactions protéine-protéine. Protocoles de la nature, 9(11), 2539.</li>
	<li>Ottman, C. (2013). Interactions protéine-protéine : un aperçu. Interactions protéine-protéine dans la découverte de médicaments.</li>
	<li>Jordán, F., Nguyen, T. P. et Liu, W. C. (2012). Étude des réseaux d’interaction protéine-protéine : une vision systémique des maladies. Briefings en génomique fonctionnelle, 11(6), 497-504.</li>
	<li>Berggård, T., Linse, S. et James, P. (2007). Méthodes de détection et d’analyse des interactions protéine-protéine. Protéomique, 7(16), 2833-2842.</li>
	<li>Gingras, A. C., Gstaiger, M., Raught, B. et Aebersold, R. (2007). Analyse de complexes protéiques par spectrométrie de masse. Biologie cellulaire moléculaire, 8(8), 645.</li>
</ol>

réseau protéique

Un organisme peut contenir des milliers de protéines différentes, et ces protéines doivent coopérer pour assurer la santé d’un organisme. Les protéines se lient à d’autres protéines et forment des complexes pour remplir leurs fonctions. De nombreuses protéines interagissent avec plusieurs autres protéines, créant un réseau complexe d’interactions protéiques.

Ces interactions peuvent être représentées par des cartes illustrant les réseaux d’interactions protéine-protéine, représentés sous forme de nœuds et de bords. Les nœuds sont des cercles représentatifs d’une protéine et les bords sont des lignes qui relient deux protéines en interaction. Ces réseaux permettent de visualiser la complexité des interactions protéine-protéine dans un système. Ces cartes peuvent inclure à la fois des interactions stables, comme celles formées dans les complexes protéiques, ainsi que des interactions transitoires. Les interactions protéiques se produisant dans une cellule, un organisme ou un contexte biologique spécifique peuvent être collectivement appelées « interactome ».

Les réseaux de protéines peuvent être étudiés à l’aide de diverses méthodes biochimiques et informatiques. L’une des premières étapes de l’étude des interactions protéiques consiste à isoler une protéine d’intérêt ainsi que les autres protéines associées. Cela peut être réalisé en marquant la protéine d'intérêt avec une étiquette d'affinité, telle qu'une étiquette histidine. Cette étiquette peut ensuite être utilisée pour séparer la protéine des autres protéines par chromatographie d’affinité. Les protéines isolées sont ensuite digérées avec une protéase, telle que la trypsine, puis analysées par chromatographie liquide-spectrométrie de masse (LC-MS). La masse peptidique peut ensuite être comparée à une base de données contenant des séquences protéiques connues pour déterminer son identité.

Par ordinateur, les interactions protéine-protéine peuvent être analysées à l’aide de bases de données ainsi que d’outils de prédiction. Il existe diverses bases de données, telles que IntAct gérées par l'EMBL-EBI, qui contiennent des interactions protéiques validées et prédites expérimentalement. D'autres outils comme STRING de l'Institut suisse de bioinformatique peuvent être utilisés pour prédire ces réseaux d'interaction.

L’étude des réseaux protéiques peut conduire à des découvertes scientifiques, comme par exemple déterminer la fonction d’une protéine inconnue. L'examen des changements dans ces réseaux peut aider à élucider les différences entre les cellules saines et malades. Ces informations peuvent également être utilisées pour des applications cruciales telles que la conception de médicaments pour le traitement de maladies. L'analyse des réseaux protéiques peut identifier des nœuds hautement connectés qui peuvent être cruciaux pour la survie cellulaire, qui peuvent être ciblés dans le cancer et les maladies où la mort cellulaire est souhaitée mais qui ne conviendraient pas à la plupart des maladies. D’un autre côté, les nœuds moins connectés qui interagissent uniquement avec quelques voies spécifiques peuvent être ciblés si une fonction cellulaire spécifique est affectée, et la conception de médicaments qui interagissent avec ces nœuds moins connectés peut entraîner moins d’effets secondaires.

Réseau protéique

Un organisme peut avoir des milliers de protéines différentes, et ces protéines doivent coopérer pour assurer la santé d’un organisme. Les protéines se lient à d’autres ...

Education

Enseignement

JoVE Core

Cell Biology

Biologie cellulaire

Unit 1

Unité 1

Protein Function

Fonction des protéines

KEY TERMS AND CONCEPTS

TERMES ET CONCEPTS CLÉS

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

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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

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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

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HS-LS1-3

Mapping Protein Interaction Networks

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