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

אורגניזם אחד יכול להכיל אלפי חלבונים שונים, ורוב החלבונים האלה חייבים לתקשר עם חלבונים אחרים כדי לבצע את תפקידיהם.
לחלבונים רבים יש שותפי קישור מרובים, מה שיוצר רשת מורכבת של אינטראקציות חלבוניות.
טכניקות מעבדה שונות, כולל שיטות ביוכימיות וחישוביות, מסייעות למדענים להבין את רשתות החלבונים האלה.
תיוג זיקה הוא שיטה המשמשת לעתים קרובות לבידוד חלבון יחד עם מולקולות אינטראקציה אחרות. תג זיקה הוא מוטיב של חומצת אמינו המתווסף גנטית לחלבון המעניין. תג זה יכול לשמש כדי לבודד את חלבון המטרה יחד עם חלבונים אחרים הקשורים אליו. 
חלבונים המקיימים אינטראקציה עם החלבון המתויג ניתנים לניתוח כדי לקבוע את זהותם ואת האינטראקציות החדשות שלהם.
שיטה אחת לניתוח אינטראקציות חלבונים לא ידועות אלה היא לפרק את החלבונים למקטעים קצרים ולנתח באמצעות ספקטרומטר מסות כדי לקבוע את רצפי חומצות האמינו. ניתן להשוות רצפים אלה למסדי נתונים קיימים של רצפי חלבונים כדי לזהות חלבונים קשורים לא ידועים. 
בנוסף, מאגרי מידע הזמינים באופן חופשי, כגון IntAct, כוללים נתוני אינטראקציה בין חלבון לחלבון שהועלו על ידי חוקרים ברחבי העולם זמינים להשוואה. מאגרי מידע אחרים, יחד עם מספר גדל והולך של כלים ביואינפורמטיים מתקדמים, יכולים לשמש לחיזוי אינטראקציות מולקולריות של חלבון לא ידוע
מפות רשת של אינטראקציה בין חלבונים לחלבונים משמשות כדי להמחיש את האינטראקציות האלה בין חלבונים בתא. המעגלים הם צמתים, המייצגים חלבון מסוים, וקווים הם קצוות, המחברים חלבון לחלבונים אחרים המקיימים אינטראקציה. 
בחינת מפות אינטראקציה של חלבונים יכולה לסייע בחיזוי תפקודי החלבון. אם תבנית האינטראקציה של חלבון לא ידוע של קצוות חיבור דומה לזו של צומת אחר, שני צמתים אלה עשויים לפעול באופן דומה.
חלק מהצמתים יופיעו כרכזות מקושרות מאוד, שהמחקר שלהן עשוי להוביל לגילוי מנגנונים בסיסיים לשמירה על בריאות התא ובכך לסייע בפיתוח תרופות.

<ol>
	<li>אלברטס ואחרים, מהדורה שישית; עמודים 166-169</li>
	<li>מוריס, J. H., Knudsen, G. M., Verschueren, E., Johnson, J. R., Cimermancic, P., Greninger, A. L., & Pico, A. R. (2014). טיהור זיקה – ספקטרומטריית מסות וניתוח רשתות להבנת אינטראקציות חלבון-חלבון. פרוטוקולי טבע, 9(11), 2539.</li>
	<li>אוטמן, ג. (2013). אינטראקציות חלבון-חלבון: סקירה כללית. אינטראקציות חלבון-חלבון בגילוי תרופות.</li>
	<li>Jordán, F., Nguyen, T. P., &�u, W. C. (2012). חקר רשתות אינטראקציה חלבון-חלבון: מבט מערכתי על מחלות. תקצירים בגנומיקה פונקציונלית, 11(6), 497-504.</li>
	<li>Berggård, T., Linse, S., & James, P. (2007). שיטות לזיהוי וניתוח אינטראקציות חלבון-חלבון. פרוטאומיקה, 7(16), 2833-2842.</li>
	<li>Gingras, A. C., Gstaiger, M., Raught, B., & Aebersold, R. (2007). ניתוח מתחמי חלבונים באמצעות ספקטרומטריית מסות. ביקורות טבע ביולוגיה מולקולרית של התא, 8(8), 645.</li>
</ol>

רשתות חלבונים

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לאורגניזם יכולים להיות אלפי חלבונים שונים, וחלבונים אלה חייבים לשתף פעולה כדי להבטיח את בריאותו של אורגניזם. חלבונים נקשרים לחלבונים אחרים ויוצרים קומפלקסים כדי לבצע את תפקידיהם. חלבונים רבים מקיימים אינטראקציה עם חלבונים רבים אחרים ויוצרים רשת מורכבת של אינטראקציות חלבון.

ניתן לייצג אינטראקציות אלו באמצעות מפות המתארות רשתות אינטראקציה בין חלבון לחלבון, המיוצגות כצמתים וקצוות. צמתים הם עיגולים המייצגים חלבון, וקצוות הם קווים המחברים בין שני חלבונים המקיימים אינטראקציה. רשתות אלו מספקות דרך לדמיין את המורכבות של אינטראקציות חלבון-חלבון במערכת. מפות אלו יכולות לכלול גם אינטראקציות יציבות, כמו אלו שנוצרות בקומפלקסים של חלבונים, וגם אינטראקציות חולפות. אינטראקציות החלבון המתרחשות בתא, באורגניזם או בהקשר ביולוגי ספציפי יכולות להיקרא ביחד "אינטראקטום".

ניתן ללמוד רשתות חלבון באמצעות שיטות ביוכימיות וחישוביות שונות. אחד השלבים הראשונים בחקירת אינטראקציות חלבון הוא לבודד חלבון הנתון יחד עם שאר החלבונים הקשורים. ניתן לבצע זאת על ידי תיוג החלבון הנתון בתג זיקה, כגון תג היסטידין. לאחר מכן ניתן להשתמש בתג זה כדי להפריד את החלבון יחד עם שאר החלבונים באמצעות כרומטוגרפיה זיקה. לאחר מכן חלבונים מבודדים מתעכלים עם פרוטאז, כגון טריפסין, ולאחר מכן מנותחים באמצעות כרומטוגרפיה נוזלית-ספקטרומטריית מסה (LC-MS). לאחר מכן ניתן להשוות את מסת הפפטידים למסד נתונים עם רצפי חלבונים ידועים כדי לקבוע את זהותה.

מבחינה חישובית, ניתן לנתח אינטראקציות חלבון-חלבון באמצעות מסדי נתונים וכן כלי חיזוי. ישנם מסדי נתונים שונים, כגון IntAct המנוהל על ידי EMBL-EBI, המורכבים מאינטראקציות חלבון מאומתות ונחזו בניסוי. ניתן להשתמש בכלים אחרים כמו STRING של המכון השוויצרי לביואינפורמטיקה כדי לחזות את רשתות האינטראקציה הללו.

חקר רשתות חלבונים יכול להוביל לתגליות מדעיות, כמו קביעת תפקידו של חלבון לא ידוע. בחינת השינויים ברשתות אלו יכולה לסייע בבירור ההבדלים בין תאים בריאים לחולים. מידע זה יכול לשמש גם עבור יישומים חיוניים כגון עיצוב תרופות לטיפול במחלות. ניתוח של רשתות חלבונים יכול לזהות צמתים מחוברים מאוד שעשויים להיות חיוניים להישרדות תאית, שיכולים להיות ממוקדים בסרטן ובמחלות שבהן רצוי מוות של תאים, אך לא יתאים לרוב המחלות. מצד שני, צמתים פחות מחוברים שרק מקיימים אינטראקציה עם כמה מסלולים ספציפיים עשויים להיות ממוקדים אם תפקוד תא מסוים מושפע, ותכנון תרופות המתקשרות עם צמתים פחות מחוברים אלה עשוי להוביל לפחות תופעות לוואי.

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אורגניזם יכול להכיל אלפי חלבונים שונים, וחלבונים אלה חייבים לשתף פעולה כדי להבטיח את בריאותו של אורגניזם. חלבונים נקשרים לאחרים ...

Education

JoVE Core

Cell Biology

ביולוגיה של התא

Unit 1

יחידה 1

Protein Function

תפקוד חלבונים

KEY TERMS AND CONCEPTS

מונחים ומושגים מרכזיים

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 Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

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

Background
Cells represent the most basic biological units of all organisms, whether it be simple, single-celled organisms like bacteria, or large, ...

Visualizing Onion and Cheek Cells
ExpandImmediately before the experiment, wash and peel onion bulbs for the class.
Remove the entire brown outer skin and ...

Visualizing Onion and Human Cells
ExpandIn this experiment you will prepare different types of cells from a plant and animal, onion and human ...

What are Cells?

Cell Diversity

The concept of a cell started with microscopic observations of dead cork tissue by Robert Hooke in 1665. Hooke coined the term &#34;cell&#34; based on the ...

Cytoplasm

The cytoplasm consists of organelles and a framework of protein scaffolds called the cytoskeleton suspended in an aqueous solution, the cytosol. The ...

The Nucleus

The nucleus is a membrane-bound organelle that acts as a control center in a eukaryotic cell. It contains chromosomal DNA, which controls gene expression ...

The Central Dogma

The DNA Helix

Nucleic Acids

DNA as a Genetic Template

Structure of a Gene

A gene is the fundamental unit of heredity. Every individual has two copies of each gene, one inherited from each parent. Although most people contain the ...

Chromosome Structure

Base-pairing and DNA Repair

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised&#160; of nucleotides and proteins are ...

RNA Structure

The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form ...

Protein Families

Types of RNA

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 ...

Intrinsically Disordered Proteins

Ribosomes

Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that ...

Protein Complex Assembly

Protein and Protein Structures

Conjugated Proteins

Proteins: From Genes to Degradation

Amyloid Fibrils

What are Proteins?

Proteins are polymers of amino acids linked together by peptide bonds. Proteins and polypeptides are interchangeably used to refer to long chains of amino ...

Ligand Binding Sites

Protein Organization

Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular ...

Protein-Protein Interfaces

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to ...

Conserved Binding Sites

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.]

Levels of Organization

Biological organization is the classification of biological structures, ranging from atoms at the bottom of the hierarchy to the Earth&#x27;s biosphere. ...

Animal and Plant Cell Structure

Animal and plant cells not only differ in their structure, function, and mode of nutrition but also in how they reproduce, specialize, and organize into ...

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

Structural Organization of the Human Body: An Overview

It is convenient to consider the body&#39;s structures in terms of fundamental levels of organization that increase in complexity: subatomic particles, ...

Overview of Human Digestion

The human body contains a monogastric digestive system. In a monogastric digestive system, the stomach only contains one chamber in which it digests food. ...

Anatomy of the Intestines

Although digestion of proteins, carbohydrates, and lipids may begin in the stomach, it is completed in the intestine. The absorption of nutrients, water, ...

Accessory Organs

Accessory organs are those that participate in the digestion of food but do not come into direct contact with it like the mouth, stomach, or intestine do. ...

Lipid Digestion

Lipids are large molecules that are generally not water-soluble. Since most of the digestive enzymes in the human body are water-based, there are specific ...

Protein Digestion

Protein digestion begins in the stomach, where the highly acidic environment can easily disrupt protein structure by exposing the peptide bonds of ...

Carbohydrate Digestion

Carbohydrate digestion and metabolism break down simple and complex carbohydrates from food into saccharides (i.e., sugars) for the body to use as energy. ...

What is a Nervous System?

Overview

The nervous system is the collection of specialized cells responsible for maintaining an organism&rsquo;s internal environment and coordinating ...

The Parasympathetic Nervous System

Overview

The parasympathetic nervous system is one of the two major divisions of the autonomic nervous system. This parasympathetic system is responsible ...

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 ...

What is a Sensory System?

Sensory systems detect stimuli&mdash;such as light and sound waves&mdash;and transduce them into neural signals that can be interpreted by the nervous ...

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?

Overview

The adult human skeleton comprises 206 bones that are connected through cartilage, tendons, and ligaments. The skeleton provides a rigid ...

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

An Introduction to the Zebrafish: Danio rerio

Zebrafish (Danio rerio) are small freshwater fish that are used as model organisms for biomedical research. The many strengths of these fish include their ...

Physiology of the Circulatory System

Homeostasis
Conditions in the external environment of an organism can change rapidly and drastically. To survive, organisms must maintain a fairly ...

Anatomy of the Circulatory System

The human circulatory system consists of blood, blood vessels that carry blood away from the heart, around the body, and back to the heart, and the heart ...

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

Anatomy of the Heart

The human heart is made up of three layers of tissue that are surrounded by the pericardium, a membrane that protects and confines the heart. The ...

Measuring Circulatory System Function in Humans
ExpandBefore starting the experiment go to the front of the room and collect an alcohol swab, a ...

Blood Flow

Blood is pumped by the heart into the aorta, the largest artery in the body, and then into increasingly smaller arteries, arterioles, and capillaries. The ...

What Are Osmoregulation and Excretion?

Organisms must keep bodily fluids at a constant temperature and pH while maintaining specific solute concentrations in order to support life functions. ...

Blood Withdrawal I

Source: Kay Stewart, RVT, RLATG, CMAR; Valerie A. Schroeder, RVT, RLATG. University of Notre Dame, IN
Blood collection is a common requirement for ...

Kidney Structure

The kidneys are two large bean-shaped organs located in the upper abdomen. They filter the blood several times a day to remove toxins and rebalance water ...

Blood Withdrawal II

Source: Kay Stewart, RVT, RLATG, CMAR; Valerie A. Schroeder, RVT, RLATG. University of Notre Dame, IN
The collection of blood from mice and rats for ...

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

Spermatogenesis is the process by which haploid sperm cells are produced in the male testes. It starts with stem cells located close to the outer rim of ...

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, ...

pH Homeostasis

Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because ...

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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