Name: allosteric switching in multimeric proteins
Uploaded: 2020-11-23T11:47:34.000Z
Duration: 1 min 58 s
Channel: JoVE

K12 Standards

Tennessee Academic Standards

High School

Biology

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

From Molecules to Organisms: Structures and Processes

BIO1.LS1.3

Cooperative Allosteric Transitions

Beaucoup de protéines ont plusieurs sous-unités où chacune contient un site de liaison au ligand distinct. Lorsqu'une molécule est appelée modulateur se lie à l'une des sous-unités, elle déclenche un changement conformationnel dans les sites de liaison des autres sous-unités, modifiant leur affinité pour leurs ligands respectifs. C'est ce qu'on appelle une transition allostérique coopérative et peut être expliquée par plusieurs modèles théoriques.Le modèle concerté ou du tout ou rien suppose que toutes les sous-unités existent ensemble dans une conformation off ou on. Une liaison peut se produire sous n'importe quelle forme. Cependant, l'état on a une affinité plus élevée pour le ligand que l'état off.Lorsqu'un ligand se lie à l'une des sous-unités, il favorise la transformation simultanée de tous les sites liaison à la forme de haute affinité. La coopération peut aussi être expliquée par le modèle séquentiel, qui suppose que chaque sous-unité peut exister indépendamment dans un état d'affinité élevé ou faible mais est plus susceptible d'être dans l'état de haute affinité lorsque le ligand est lié à l'une des sous-unités. Les sites de liaison des protéines allostériques sont généralement un mélange de segments flexibles et fixes de la chaîne des acides aminés.Lorsqu'un ligand se lie, ces parties instables sont stabilisés dans une conformation particulière. Et cela affecte la forme des sites de liaison sur les autres sous-unités. L'hémoglobine est un exemple d'une protéine tétramère qui subit une transition allostérique coopérative quand l'oxygène s'y lie.Chaque sous-unité d'hémoglobine possède un seul site de liaison. Lorsqu'une molécule d'oxygène se lie à une seule sous-unité, la coopération augmente l'affinité pour l'oxygène sur les sites liaison restants, facilitant ainsi, la liaison de l'oxygène à une molécule d'hémoglobine qui a déjà de l'oxygène lié à elle.

<ol>
	<li>Cornish‐Bowden, A. (2014), Comprendre les interactions allostériques et coopératives dans les enzymes. FEBS J, 281 : 621-632. doi :10.1111/febs.12469</li>
	<li>Alberts et al., 6e édition ; pages 152-153</li>
	<li>Principes de biochimie de Lehninger, 5e édition, pages 162,165</li>
</ol>

transitions allostériques coopératives

Des transitions allostériques coopératives peuvent se produire dans les protéines multimères, où chaque sous-unité de la protéine possède son propre site de liaison au ligand. Lorsqu'un ligand se lie à l'une de ces sous-unités, il déclenche un changement conformationnel qui affecte les sites de liaison des autres sous-unités ; cela peut modifier l'affinité des autres sites pour leurs ligands respectifs. La capacité de la protéine à modifier la forme de son site de liaison est attribuée à la présence d’un mélange de segments flexibles et stables dans la structure. Une molécule qui déclenche ce changement est appelée modulateur.

Deux modèles sont souvent utilisés pour expliquer la coopérativité dans les protéines multimériques : le modèle concerté et le modèle séquentiel. Le modèle concerté, également connu sous le nom de modèle tout ou rien, émet l’hypothèse que toutes les sous-unités d’une protéine multimérique commutent simultanément entre les conformations « on » et « off ». Sous la forme « on », les sites de liaison ont une forte affinité pour leurs ligands respectifs, et sous la forme « off », les sites de liaison ont une faible affinité. Lorsqu'un ligand se lie à l'une des sous-unités, il favorise la conversion vers la forme de haute affinité, modifiant simultanément la conformation de tous les autres sites de liaison de la protéine. Bien qu'un ligand puisse se lier à l'une ou l'autre forme, il lui est plus facile de se lier sous la forme à haute affinité.

Le modèle séquentiel suppose que chaque sous-unité d’une protéine multimérique peut exister indépendamment dans une conformation « on » ou « off », c’est-à-dire sous la forme de faible ou de haute affinité, quel que soit l’état des autres sous-unités. La liaison d'un ligand à une sous-unité modifie l'équilibre entre les formes de faible et de haute affinité, de sorte qu'il est plus probable que la sous-unité soit sous une forme de haute affinité. De plus, la liaison d'un ligand sur une sous-unité modifie l'équilibre des autres sous-unités de la protéine. Cela augmente la probabilité qu'une fois qu'un ligand est lié, un autre ligand se lie à une sous-unité différente. Cette coopérativité augmente la sensibilité de la protéine à la concentration du ligand. La liaison d'un ligand sur un site unique peut modifier l'affinité sur la molécule protéique entière, permettant ainsi une réponse rapide à de faibles concentrations.

Transitions allostériques coopératives

Des transitions allostériques coopératives peuvent se produire dans les protéines multimériques, où chaque sous-unité de la protéine a son propre site de liaison au ligand. Lorsqu’un ligand ...

Education

Enseignement

JoVE Core

Molecular Biology

Biologie moléculaire

Unit 1

Unité 1

Protein Function

Fonction des protéines

KEY TERMS AND CONCEPTS

TERMES ET CONCEPTS CLÉS

allosteric switching in multimeric proteins

Allosteric switching in multimeric proteins helps explain how ligand binding at one site can change the behavior of the whole protein. In these proteins, each subunit has its own ligand-binding site. When a ligand binds to one subunit, it can cause a shape change that affects the other subunits and their binding sites.

This change in shape comes from the protein’s structure, which includes both flexible and stable segments. A molecule that causes the shift is called a modulator. Because the binding sites can change shape, the protein can alter the affinity of other sites for their ligands.

Two common models describe this cooperativity in multimeric proteins. The concerted model, also called the all-or-none model, says that all subunits switch together between an “on” state and an “off” state. In the on state, the sites have high affinity. In the off state, they have low affinity. A ligand can bind to either form, but binding is easier in the high-affinity form.

The sequential model takes a different view. It assumes that each subunit can be in an on or off conformation on its own, no matter what the other subunits are doing. When a ligand binds to one subunit, it shifts the balance toward the high-affinity form in that subunit and makes it more likely for other subunits to follow.

This cooperativity makes the protein more sensitive to ligand concentration. After one ligand binds, another ligand is more likely to bind at a different subunit. As a result, a single binding event can change the affinity of the entire protein and support a rapid response even at low ligand levels.

Allosteric Switching in Multimeric Proteins

allosteric-switching-in-multimeric-proteins

ligand binding sites

How Ligands Attach to Proteins

Ligands attach to proteins at specific binding sites on the protein surface. These sites let proteins interact with other molecules or ions and help them carry out important cell functions. Although many possible ligands may be nearby, only a matching ligand can bind to a given protein. A ligand-binding site has a shape and chemical pattern that fit its ligand. This fit comes from the protein’s amino acid chain, which gives the site its structure and reactivity. The ligand stays in place...

protein-protein interfaces

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conserved binding sites

Predicting Protein Ligand-Binding Pockets

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the equilibrium binding constant and binding strength

the-equilibrium-binding-constant-and-binding-strength

Measuring Protein-Ligand Binding Strength

Protein-ligand binding strength can be measured with the equilibrium binding constant, Kb. This value describes how strongly a protein binds a ligand when the reaction has reached equilibrium. In a bound complex, the protein and ligand are joined as PL, while P and L are the unbound forms. Kb can be determined in two main ways. One approach uses equilibrium concentrations. The other uses reaction kinetics, which are the rates of binding and unbinding. Kb can also be related to the binding rate...

cofactors and coenzymes

Protein Helpers: Cofactors and Coenzymes

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allosteric regulation

How Allosteric Control Changes Enzymes

Allosteric control changes how enzymes work by using a site other than the active site. A small molecule binds to this separate allosteric site and changes the enzyme’s shape. That shape change can alter how well the enzyme binds its substrate and how fast the reaction runs. Many enzymes use this kind of regulation to turn activity up or down when the cell needs it. In some cases, the allosteric molecule acts as an activator and improves enzyme function. In other cases, it acts as an inhibitor...

ligand binding and linkage

Allosteric Proteins: Positive and Negative Effects

Allosteric proteins have more than one ligand binding site. A ligand is a molecule that binds to a protein. When a ligand binds at one site, it can affect binding at the other sites. These sites are called coupled or linked because they influence one another. In enzymes, the site that binds the substrate is the active site. The other site is the regulatory site. When a ligand binds to the regulatory site, it can change the protein’s shape. This conformational change can then alter how the...

cooperative allosteric transitions

Allosteric switching in multimeric proteins helps explain how ligand binding at one site can change the behavior of the whole protein. In these proteins, each subunit has its own ligand-binding site. When a ligand binds to one subunit, it can cause a shape change that affects the other subunits and their binding sites. This change in shape comes from the protein’s structure, which includes both flexible and stable segments. A molecule that causes the shift is called a modulator. Because the...

phosphorylation

Phosphorylation in Cell Signaling

Phosphorylation is a key step in cell signaling. It changes how a molecule behaves by adding a phosphate group. In many cells, this modification helps control activity, shape, and interactions with other molecules. Phosphorylation is carried out by enzymes called kinases. These enzymes transfer a phosphate group to a target molecule. A phosphatase can remove that phosphate group and reverse the change. Together, kinases and phosphatases help cells turn signals on and off in a controlled way. <br...

protein kinases and phosphatases

Phosphorylation Switches in Protein Control

Protein control often depends on chemical changes that alter a protein’s charge, shape, and conformation. These changes can include phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis. In cells, these modifications are usually driven by enzymes. Phosphorylation is one of the most important protein modifications. It adds a phosphate group to a protein and often changes how that protein works. A family of enzymes called kinases...

gtpases and their regulation

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covalently linked protein regulators

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protein complexes with interchangeable parts

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mechanical protein functions

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structural protein function

Collagen and the Cell Skeleton

Structural proteins give cells and tissues shape, support, and strength. They help build bones, cartilage, hair, and muscles. Important examples include collagen, actin, myosin, and keratin. Collagen is the most abundant protein in mammals. It is found throughout the body. In skin, ligaments, and tendons, collagen adds tensile strength and elasticity. In bones and teeth, it helps form hard, load-bearing tissue through mineralization. Collagen also does more than provide support. It can...

protein networks

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allosteric proteins-atcase

ATCase Feedback Inhibition in Pyrimidine Synthesis

ATCase is a key enzyme in pyrimidine synthesis. It is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to form N-carbamoyl-L-aspartate. This reaction starts the pathway that makes pyrimidines. ATCase is regulated by feedback inhibition. The end products UTP and CTP bind to the enzyme and reduce its activity when pyrimidine levels are high compared with purines in the cell. This binding at one site affects the linked catalytic site, which helps keep...

key terms and concepts

Learn how ligand binding can switch multimeric proteins between low- and high-affinity states through concerted and sequential cooperativity models.

Allosteric Switching in Multimeric Proteins | JoVE K12

molecular biology

JoVE Core Biologie Moléculaire illustre les processus moléculaires au sein de la cellule grâce à des leçons vidéos claires et concises. Les applications de ces concepts sont ensuite démontrées grâce à des expériences concrètes en laboratoire.

Arizona Science Standards

Life Science

HS+B.L1

HS+B.L1U1.5

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Compare and contrast existing models, identify patterns, and use structural and functional evidence to analyze the characteristics of life. Engage in argument about the designation of viruses as non-living based on these characteristics.
EXPLANATION: Students begin to develop patterns of living and non-living organisms in kindergarten and build on detailed characteristics of different classifications of living organisms throughout elementary and middle school. Biology 1 discussions introduce viral particles and viral cycles, building on student understanding of living organisms to engage in an argument regarding the classification of a viral particle as either living or non-living.

BIO1.LS1.1

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Evaluate comparative models of various cell types with a focus on organic molecules that make up cellular structures.
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BIO1.LS1.2

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Organization of Genes

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Replication in Eukaryotes

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Transcription

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Lesson: Translation
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MicroRNAs

siRNA - Small Interfering RNAs

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piRNA - Piwi-interacting RNAs

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conservation-of-protein-domains-over-different-proteins

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Conjugated Proteins

Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with ...

Allosteric Proteins-ATCase

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Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand ...

Antibody Structure

Phosphorylation

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their ...

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, ...

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism&#39;s survival. Most PPIs ...

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell ...

Conserved Binding Sites

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Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an ...

The Equilibrium Binding Constant and Binding Strength

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Integrate evidence to develop a structural model of a DNA molecule. Using the model, develop and communicate an explanation for how DNA serves as a template for self-replication and encodes biological information.
EXPLANATION: Discussions of DNA in earlier grades have been limited to discussions of genes and the role of genes in the appearance and activities of an organism. Biology 1 represents a student's introduction to a molecular model of a DNA as well as the organization of DNA into genes and genes subsequently into chromosomes. Students should address interactions between genes in proteins which regulate both the shape and reproduction of DNA molecules. It is important to note that not all segments of DNA are transcribed for proteins. Portions of DNA are involved in regulating the expression of genes or affect the structure of the chromosomes (replication origin, centromeres, and telomeres).

Allosteric Switching in Multimeric Proteins

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