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

Um único organismo pode conter milhares de proteínas diferentes. E a maioria destas proteínas deve interagir com outras proteínas a fim executar suas funções. Muitas proteínas têm múltiplos parceiros de ligação, o que resulta em uma rede complexa de ligações de proteínas.Várias técnicas laboratoriais, incluindo ambos métodos bioquímicos e computacionais, ajudam cientistas a compreender estas redes de proteínas. A marcação por afinidade é um método muitas vezes usado para isolar uma proteína juntamente com qualquer outra interação de moléculas. Uma etiqueta da afinidade é um motivo do aminoácido que é adicionado geneticamente à proteína do interesse.Esta etiqueta pode ser usada para isolar a proteína alvo ao longo de com outras proteínas associadas a ela. Proteínas interagindo com a proteína etiquetada podem ser analisadas para determinar sua identidade e novas interações. Um método de analisar estas interações de proteína desconhecidas é quebrar as proteínas em segmentos curtos e analisar com um espectrômetro de massa para determinar as sequências de aminoácidos.Estas sequências podem ser comparadas à sequência de proteínas existentes em bases de dados para identificar proteínas associadas desconhecidas. Adicionalmente, bases de dados livremente disponíveis, tais como IntAct, têm dados das interações proteína-proteína carregados por investigadores de todo mundo disponível para a comparação. Outras bases de dados, junto com um número crescente de ferramentas bioinformáticas avançadas, pode ser usado para predizer as interações moleculares de uma proteína desconhecida.Os mapas de rede de interação proteína-proteína são usados para visualizar estas interações entre proteínas em uma célula. Os círculos são nós que representam uma proteína particular. E as linhas são bordas que conectam uma proteína às outras proteínas interagindo.Examinar mapas de interação de proteína pode ajudar predizer as funções da proteína. Se um padrão desconhecido da interação da proteína de extremidades conectando é similar àquele de outro nó, estes dois nós podem agir similarmente. Alguns nós aparecerão como cubos altamente conectados, o estudo deles podem levar à descoberta de mecanismos fundamentais para manter a saúde da célula, ajudando assim no desenvolvimento de drogas.

<ol>
	<li>Alberts et al., 6ª edição; 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). Purificação de afinidade - espectrometria de massa e análise de rede para entender as interações proteína-proteína. Protocolos da natureza, 9(11), 2539.</li>
	<li>Ottman, C. (2013). Interações proteína-proteína: uma visão geral. Interações proteína-proteína na descoberta de medicamentos.</li>
	<li>Jordán, F., Nguyen, T. P., & Liu, W. C. (2012). Estudando redes de interação proteína-proteína: uma visão sistêmica sobre doenças. Briefings em genômica funcional, 11(6), 497-504.</li>
	<li>Berggård, T., Linse, S., & James, P. (2007). Métodos para a detecção e análise de interações proteína-proteína. Proteômica, 7(16), 2833-2842.</li>
	<li>Gingras, A. C., Gstaiger, M., Raught, B., & Aebersold, R. (2007). Análise de complexos proteicos usando espectrometria de massa. Revisões da natureza Biologia celular molecular, 8(8), 645.</li>
</ol>

redes de proteínas

Um organismo pode ter milhares de proteínas diferentes, e estas proteínas devem cooperar para garantir a saúde de um organismo. As proteínas ligam-se a outras proteínas e formam complexos para desempenhar as suas funções. Muitas proteínas interagem com várias outras proteínas, criando uma rede complexa de interações proteicas. Essas interações podem ser representadas por meio de mapas que representam redes de interação proteína-proteína, representadas como nós e arestas. Os nós são círculos representativos de uma proteína e as arestas são linhas que conectam duas proteínas em interação. Essas redes fornecem uma maneira de visualizar a complexidade das interações proteína-proteína em um sistema. Esses mapas podem incluir tanto interações estáveis, como aquelas formadas em complexos proteicos, quanto interações transitórias. As interações proteicas que ocorrem em uma célula, em um organismo ou em um contexto biológico específico podem ser chamadas coletivamente de “interactoma”. Redes de proteínas podem ser estudadas usando vários métodos bioquímicos e computacionais. Um dos primeiros passos no estudo das interações proteicas é isolar uma proteína de interesse juntamente com as outras proteínas associadas. Isto pode ser realizado marcando a proteína de interesse com um marcador de afinidade, tal como um marcador de histidina. Esta etiqueta pode então ser usada para separar a proteína junto com as outras proteínas usando cromatografia de afinidade. As proteínas isoladas são então digeridas com uma protease, como a tripsina, e depois analisadas usando cromatografia líquida-espectrometria de massa (LC-MS). A massa do peptídeo pode então ser comparada a um banco de dados com sequências proteicas conhecidas para determinar sua identidade. Computacionalmente, as interações proteína-proteína podem ser analisadas usando bancos de dados e também ferramentas de predição. Existem vários bancos de dados, como o IntAct gerenciado pela EMBL-EBI, que consistem em interações proteicas previstas e validadas experimentalmente. Outras ferramentas como o STRING do Instituto Suíço de Bioinformática podem ser usadas para prever essas redes de interação. O estudo de redes proteicas pode levar a descobertas científicas, como a determinação da função de uma proteína desconhecida. Examinar as mudanças nessas redes pode ajudar a elucidar as diferenças entre células saudáveis e doentes. Esta informação também pode ser usada para aplicações cruciais, como a concepção de medicamentos para o tratamento de doenças. A análise de redes de proteínas pode identificar nós altamente conectados que podem ser cruciais para a sobrevivência celular, que podem ser alvo de câncer e doenças onde a morte celular é desejada, mas seria inadequada para a maioria das doenças. Por outro lado, nós menos conectados que interagem apenas com algumas vias específicas podem ser alvo se uma função celular específica for afetada, e o desenvolvimento de medicamentos que interajam com esses nós menos conectados pode levar a menos efeitos colaterais.

Redes de Proteínas

Um organismo pode ter milhares de proteínas diferentes, e essas proteínas devem cooperar para garantir a saúde de um organismo. As proteínas se ligam a outras ...

Education

JoVE Core

Cell Biology

Biologia Celular

Unit 1

Unidade 1

Protein Function

Função Proteica

KEY TERMS AND CONCEPTS

TERMOS-CHAVE E CONCEITOS

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 - Biologia Celular ilustra processos celulares complexos em vídeos de animação fáceis de entender e, ao mesmo tempo, abrangentes. Esta coleção foca nos componentes e funções essenciais das células, incluindo organelas e membranas, transporte celular e energia celular. É complementado por vídeos de Cientistas em ação que demonstram a aplicação da biologia celular em experimentos de pesquisa do mundo real.

Characteristics of Life

Biology is a natural science that studies life and living organisms, including their structure, function, development, interactions, evolution, ...

https://cloudfront.jove.com/files/media/science-education/science-education-thumbs/10647.jpg

Cell Structure

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Cytoplasm

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Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse ...

Conservation of Protein Domains

Transcription

Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. ...

Globular and Fibrous Proteins

Translation

Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes ...

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Proteins: From Genes to Degradation

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Protein-Protein Interfaces

Protein Folding

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Cofactors and Coenzymes

Enzymes are proteins made of amino acids. The functional group of each constituent amino acid catalyzes a wide variety of chemical reactions via ionic ...

Cooperative Allosteric Transitions

Protein Kinases and Phosphatases

GTPases and their Regulation

Covalently Linked Protein Regulators

Protein Complexes with Interchangeable Parts

Mechanical Protein Function

Structural Protein Function

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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structural-organization-of-the-human-body-an-overview

Structural Organization of the Human Body: An Overview

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Overview of Human Digestion

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Overview

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The Parasympathetic Nervous System

Overview

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The Sympathetic Nervous System

Overview

The sympathetic nervous system&mdash;one of the two major divisions of the autonomic nervous system&mdash;is activated in times of stress. It ...

Oogenesis

In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from ...

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Fertilization

During fertilization, an egg and sperm cell fuse to create a new diploid structure. In humans, the process occurs once the egg has been released from the ...

What is the Skeletal System?

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an-introduction-to-the-zebrafish-danio-rerio

An Introduction to the Zebrafish: Danio rerio

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Physiology of the Circulatory System

Homeostasis
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Anatomy of the Circulatory System

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Measuring Blood Pressure
ExpandTo prepare for the blood pressure exercise, simply place the appropriate number of alcohol swabs, sphygmomanometers, and ...

Anatomy of the Heart

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Measuring Circulatory System Function in Humans
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Blood Flow

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What Are Osmoregulation and Excretion?

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Blood Withdrawal I

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Kidney Structure

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Blood Withdrawal II

Source: Kay Stewart, RVT, RLATG, CMAR; Valerie A. Schroeder, RVT, RLATG. University of Notre Dame, IN
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What is the Immune System?

Overview

The immune system comprises diverse biological structures and processes that protect the body from disease. These processes can be classified ...

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain ...

Spermatogenesis

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Bone Structure

Within the skeletal system, the structure of a bone, or osseous tissue, can be exemplified in a long bone, like the femur, where there are two types of ...

Breathing

The process of breathing, inhaling and exhaling, involves the coordinated movement of the chest wall, the lungs, and the muscles that move them. Two ...

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?

Maintaining homeostasis requires that the body continuously maintain its internal conditions. Each physiological condition has a particular set point, ...

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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