Name: how amino acid sequence shapes proteins
Uploaded: 2023-04-30T10:34:15.000Z
Duration: 1 min 25 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 Folding

In un peptide di nuova sintesi, le interazioni tra i suoi amminoacidi costituenti guidano il suo ripiegamento in una struttura tridimensionale stabile chiamata conformazione nativa, spesso la sua forma funzionale.
In primo luogo, la catena polipeptidica lineare si ripiega in alfa-eliche e beta-fogli attraverso il legame idrogeno tra i residui di amminoacidi.
Le catene laterali idrofobiche che sporgono dalle eliche o dai fogli beta si uniscono, rimuovendo le molecole d'acqua circostanti. Di conseguenza, il polipeptide viene impacchettato in un intermedio piegato in modo lasco con un nucleo idrofobo.
I residui polari sulla superficie creano ulteriori legami idrogeno e interazioni ioniche, mentre le cisteine adiacenti formano legami disolfuro covalenti per stabilizzare la proteina nella sua conformazione nativa.
Per le proteine con cisteine multiple, l'enzima proteina disolfuro isomerasi catalizza il rapido scambio di gruppi tiolici, consentendo la corretta formazione del legame disolfuro.
La maggior parte delle proteine non si ripiega da sola e sono aiutate dalle proteine da shock termico e dalle chaperonine.
Questi chaperoni molecolari accelerano il processo di ripiegamento legando il peptide dispiegato e impedendo l'aggregazione o fornendo un microambiente in cui il peptide può ripiegarsi nella sua conformazione nativa.

<ol>
	<li>Lodish, Harvey, et al. Biologia cellulare molecolare. 8a ed. W.H. Freeman and Company, 2016. Pagine 81-85</li>
	<li>Donald Voet e Judith G Voet Biochimica. 4a ed. JOHN WILEY & SONS, INC. 2011. Pagine 278-290</li>
	<li>Nelson e Cox, Lehninger, Principi di biochimica, 7a ed. W.H. Freeman and Company, 2016. Pagine 396-407</li>
</ol>

ripiegamento delle proteine

Le proteine sono catene di amminoacidi legate tra loro da legami peptidici. Dopo la sintesi, una proteina si ripiega assumendo una conformazione tridimensionale, fondamentale per la sua funzione biologica. Le interazioni tra i suoi amminoacidi costituenti guidano il ripiegamento delle proteine, e quindi la struttura della proteina dipende principalmente dalla sua sequenza di amminoacidi.

La struttura delle proteine è fondamentale per la sua funzione biologica

Le proteine svolgono una vasta gamma di funzioni biologiche come catalizzare reazioni chimiche, fornire difesa immunologica, conservazione, trasporto, comunicazione cellulare, movimento e supporto strutturale. La funzione di una proteina dipende principalmente dal riconoscimento e dal legame di altre molecole, in modo analogo a una serratura e una chiave. Quindi l'attività specifica di ciascuna proteina dipende dalla sua unica architettura tridimensionale.

Perché una proteina sia funzionale, deve ripiegarsi accuratamente. La maggior parte delle proteine attraversa diverse forme intermedie prima di ripiegarsi nella struttura più stabile e biologicamente attiva. Il misfolding delle proteine può compromettere il funzionamento complessivo della cellula. L'accumulo di proteine mal ripiegate o non ripiegate negli esseri umani porta alla fibrosi cistica, all'Alzheimer, al Parkinson, alla sclerosi laterale amiotrofica e alla malattia di Creutzfeldt-Jakob.

Determinanti critici della struttura delle proteine

Le proteine sono costituite da una o più catene di aminoacidi chiamate polipeptidi. Un polipeptide è sintetizzato come una catena lineare che si ripiega rapidamente su se stessa per formare una struttura tridimensionale. I termini polipeptide e proteina sono talvolta usati in modo intercambiabile, ma più comunemente un polipeptide ripiegato che può svolgere una funzione biologica è chiamato proteina. La struttura di una proteina è solitamente descritta su quattro livelli: primario, secondario, terziario e quaternario. La maggior parte dei polipeptidi si ripiega in una struttura terziaria globulare e compatta, come l'emoglobina, la proteina che trasporta l'ossigeno nel sangue. Alcune proteine, come la cheratina, formano fibre lunghe e si trovano comunemente nei capelli e nelle unghie. Le proteine globulari sono solubili in acqua, a differenza delle proteine fibrose.

La sequenza di amminoacidi nella catena polipeptidica è il determinante principale della sua struttura. La sequenza amminoacidica determina il tipo e la posizione delle strutture secondarie. Inoltre, la struttura terziaria complessiva di una proteina è prevalentemente stabilizzata da legami chimici tra le catene laterali degli amminoacidi, gli unici gruppi chimici che distinguono gli amminoacidi gli uni dagli altri. Queste catene laterali sono cariche (positivamente o negativamente), polari-scaricate o non polari.

Gli amminoacidi hanno caratteristiche fisiche e chimiche uniche a seconda dei gruppi della catena laterale. Ad esempio, gli amminoacidi polari e carichi interagiscono con l'acqua per formare legami idrogeno e sono chiamati idrofili. Al contrario, gli amminoacidi non polari evitano le interazioni con l’acqua e sono detti idrofobici. Pertanto, quando una proteina viene ripiegata in un ambiente cellulare, le catene laterali di amminoacidi idrofobici vengono sepolte nel nucleo della proteina, lontano dall'ambiente acquoso. Al contrario, le catene laterali degli amminoacidi idrofili sono esposte sulla superficie della proteina.

Gli amminoacidi idrofobici strettamente raggruppati nel nucleo proteico portano alla formazione di deboli interazioni di Van der Waals tra i gruppi della catena laterale. Queste forze di Van der Waals conferiscono maggiore stabilità alla proteina ripiegata. Gli amminoacidi polari esposti sulla superficie della proteina sono liberi di formare legami idrogeno con molecole d'acqua o altre catene laterali di amminoacidi polari. Gli amminoacidi con carica positiva e negativa sono presenti anche all'esterno della proteina, dove formano legami ionici con altri amminoacidi vicini di carica opposta.

I legami disolfuro si formano tra due gruppi sulfidrilici, o SH, sull'amminoacido cisteina. Questa è un'interazione robusta che agisce come un rinforzo sulla proteina ripiegata. I legami disolfuro bloccano la proteina ripiegata nella sua conformazione tridimensionale preferita. Il corretto ripiegamento di una proteina dipende anche da altri fattori dell'ambiente cellulare come pH, concentrazione di sali, temperatura, ecc. L'alterazione delle condizioni fisiche e chimiche in un ambiente proteico influisce sulle interazioni chimiche che tengono insieme la proteina e può causare un ripiegamento errato della proteina. oppure dispiegarsi e perdere la sua funzione biologica, un processo noto come denaturazione delle proteine.

Ripiegamento delle proteine

Le proteine sono catene di amminoacidi legati tra loro da legami peptidici. Dopo la sintesi, una proteina si ripiega in una conformazione tridimensionale, fondamentale per ...

Education

Didattica

JoVE Core

Cell Biology

Biologia cellulare

Unit 1

Unità 1

Protein Structure

Struttura delle proteine

KEY TERMS AND CONCEPTS

TERMINI E CONCETTI CHIAVE

how amino acid sequence shapes proteins

Proteins get their shape from the order of amino acids in a polypeptide chain. After a protein is made, the chain folds into a three-dimensional form that is needed for it to work. The way amino acids interact with one another guides this folding.

Protein structure matters because proteins do many jobs in cells. They can speed up chemical reactions, help with immune defense, store materials, carry substances, send cell signals, support movement, and provide structure. A protein usually works by binding to another molecule, much like a lock and key. That is why its specific three-dimensional shape is so important.

To be functional, a protein must fold correctly. Many proteins pass through several intermediate forms before reaching the most stable and biologically active shape. When proteins misfold, they can disrupt cell function. In humans, misfolded or unfolded proteins are linked with cystic fibrosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease.

Proteins are made of one or more amino acid chains called polypeptides. A polypeptide starts as a linear chain and then folds quickly into a three-dimensional structure. The words polypeptide and protein are sometimes used interchangeably, but a folded polypeptide that can do a job is usually called a protein. Protein structure is often described at four levels: primary, secondary, tertiary, and quaternary.

Most polypeptides fold into a compact, globular tertiary structure. Hemoglobin, the oxygen-carrying protein in blood, is an example. Some proteins, such as keratins, form long fibers and are found in hair and nails. Globular proteins are usually soluble in water, while fibrous proteins are not.

The amino acid sequence is the main factor that determines protein shape. It helps decide where secondary structures form and how the full tertiary structure develops. Side chains, the chemical groups that make amino acids different from one another, stabilize the folded protein. These side chains may be charged, polar but uncharged, or non-polar.

Polar and charged amino acids interact with water and are called hydrophilic. Non-polar amino acids avoid water and are called hydrophobic. When a protein folds in a cell, hydrophobic side chains are usually buried in the core, away from water, while hydrophilic side chains stay on the surface. Tight packing in the hydrophobic core creates weak Van der Waals interactions that help stabilize the structure.

Hydrophilic side chains on the outside can form hydrogen bonds with water or with other polar side chains. Positively and negatively charged amino acids can also form ionic bonds with nearby oppositely charged amino acids. Another strong bond, called a disulfide bond, forms between two sulfhydryl, or SH, groups on cysteine. This bond helps lock the protein into its most stable three-dimensional shape.

Protein folding also depends on the cell’s environment. pH, salt concentration, and temperature can affect the chemical interactions that hold a protein together. If these conditions change, a protein may misfold or unfold and lose its function. This process is called protein denaturation.

How Amino Acid Sequence Shapes Proteins

what are proteins?

Protein Building Blocks and Folding

Proteins are built from amino acids linked by peptide bonds. Long chains of amino acids are often called polypeptides, and the terms proteins and polypeptides are sometimes used the same way. In this context, polypeptides with a molecular weight below 10,000 daltons are called polypeptides, while proteins have a higher molecular weight. Very short chains with fewer than 20 amino acids are called peptides or oligopeptides. Amino acids are the basic units of proteins. Each amino acid has a...

protein organization

Protein Folding Levels and Bonds

Proteins are built from amino acids and folded into shapes that support many cell jobs. They help with DNA replication, molecular transport, catalysis, and structural support. Their function depends on how their amino acids are arranged and folded. Protein structure is organized in levels. The primary structure is the amino acid sequence in a polypeptide chain. Amino acids are joined by peptide bonds, and the chain has two ends: the amino terminus, or N-terminus, and the carboxyl terminus, or...

protein folding

Proteins get their shape from the order of amino acids in a polypeptide chain. After a protein is made, the chain folds into a three-dimensional form that is needed for it to work. The way amino acids interact with one another guides this folding. Protein structure matters because proteins do many jobs in cells. They can speed up chemical reactions, help with immune defense, store materials, carry substances, send cell signals, support movement, and provide structure. A protein usually works...

protein families

Protein Families and Superfamilies

Protein families and superfamilies group proteins with shared features. These groups help scientists organize proteins by common structure, function, or evolutionary history. The classification can show how related proteins are connected across different organisms. A protein family usually includes proteins that are closely related. A superfamily is a broader group that can include several families with more distant relationships. These categories help explain why some proteins share similar...

conservation of protein domains

Protein Domains Shared Across Proteins

Protein domains are shared structural and functional parts of proteins. A domain is a region that can often be found in more than one protein, even when the full proteins are different. This conservation means that a protein domain may keep a similar shape or role across related proteins. Because of that, scientists can compare proteins by looking for domains that stay the same. Conserved domains help reveal how proteins are related and how they may work. The topic of protein domain...

globular and fibrous proteins

Protein Shapes: Globular vs Fibrous

Proteins can have globular or fibrous shapes, and these shapes help explain how they work in the body. Globular proteins are compact and usually fold into rounded forms. Fibrous proteins are long, extended molecules that often provide support and structure. The shape of a protein is tied to its function. Globular proteins often take part in chemical jobs in cells, while fibrous proteins are better suited for strength and stability. These structural differences make the two groups easy to...

intrinsically disordered proteins

Flexible Protein Regions and Disorder

Intrinsically disordered proteins have flexible regions that do not settle into one fixed shape. Instead, these proteins can remain dynamic and change form as they move through the cell. This flexibility is an important part of their structure and function. Many proteins need a stable folded shape to work properly. Intrinsically disordered proteins are different because they may lack a single rigid structure under normal conditions. Their shifting shape can help them take part in cell...

protein complex assembly

Protein Complex Formation and Function

Protein complex formation explains how proteins join together to carry out specific jobs in cells. These groups are called protein complexes, and they can form in more than one way. Some complexes are homomeric, which means they contain the same kind of protein subunit. Others are heteromeric, which means they contain different protein subunits. The assembly process helps show how protein shape and subunit choice affect function. When proteins combine, the resulting complex can behave...

conjugated proteins

Conjugated Proteins and Their Bound Groups

Conjugated proteins are proteins that include a nonprotein part called a prosthetic group. This added group helps give the protein its full structure or function. The video explains how the protein part and the bound group work together. Several common types of conjugated proteins are named by the kind of group attached. Nucleoproteins contain nucleic acids. Glycoproteins contain carbohydrate groups, and lipoproteins contain lipid groups. Other examples include phosphoproteins, which have...

amyloid fibrils

Amyloid Fibrils and Protein Aggregation

Amyloid fibrils are protein aggregates with a very specific structure. They are made when proteins misfold and stick together in long, ordered fibers. This structure makes them different from many other protein clumps. Amyloid fibrils are important in biology because they are linked to protein aggregation. Protein aggregation means proteins build up into groups instead of staying properly folded and separate. In many cases, this process is associated with disease and abnormal cell function. <br...

key terms and concepts

Learn how amino acid sequence, side-chain interactions, and cell conditions shape protein structure, stability, and function in high school biology.

How Amino Acid Sequence Shapes Proteins | 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.

new-york-state-science-learning-standards

New York State Science Learning Standards

Structure and Function

HS-LS1-1.

Characteristics of Life

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Ribosomes

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Protein and Protein Structures

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GTPases and their Regulation

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protein-complexes-with-interchangeable-parts

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Mechanical Protein Function

Structural Protein Function

Protein Networks

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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HS-LS1-2

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pH Homeostasis

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HS-LS1-3

How Amino Acid Sequence Shapes Proteins

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