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 a newly synthesized peptide, interactions between its constituent amino acids guide its folding into a stable three-dimensional structure called the native conformation, often its functional form.
First, the linear polypeptide chain folds into alpha-helices and beta-sheets through hydrogen bonding between amino acid residues.
Hydrophobic side chains jutting out of the helices or beta-sheets come together, removing surrounding water molecules. As a result, the polypeptide is packed into a loosely folded intermediate with a hydrophobic core.
Polar residues on the surface make additional hydrogen bonds and ionic interactions, while adjacent cysteines form covalent disulfide bonds to stabilize the protein in its native conformation.
For proteins with multiple cysteines, protein disulfide isomerase enzyme catalyzes the rapid exchange of thiol groups, enabling correct disulfide bond formation.
Most proteins do not fold by themselves and are helped by heat shock proteins and chaperonins.
These molecular chaperones speed up the folding process by binding the unfolded peptide and preventing aggregation or providing a microenvironment where the peptide can fold into its native conformation.

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 its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing immunological defense, storage, transport, cellular communication, movement, and structural support. A protein&#39;s function mostly depends on recognizing and binding other molecules, analogous to a lock and key. Hence the specific activity of each protein depends on its unique three-dimensional architecture.
For a protein to be functional, it must fold accurately. Most proteins go through several intermediate forms before folding into the most stable, biologically active structure. Protein misfolding can impair the overall functioning of the cell.&#160; Accumulation of misfolded or unfolded proteins in humans leads to cystic fibrosis, Alzheimer&#39;s, Parkinson&#39;s, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease.
Critical Determinants of Protein Structure
Proteins are made up of one or more chains of amino acids called polypeptides. A polypeptide is synthesized as a linear chain that rapidly folds upon itself to form a three-dimensional structure. The terms polypeptide and protein are sometimes used interchangeably, but most commonly, a folded polypeptide that can perform a biological function is called a protein. A protein structure is usually described on four levels: primary, secondary, tertiary, and quaternary. Most polypeptides fold into an overall compact, globular tertiary structure, such as hemoglobin, the oxygen-carrying protein in the blood. Some proteins like keratins form long fibers and are commonly found in hair and nails. Globular proteins are soluble in water, unlike fibrous proteins.
The sequence of amino acids in the polypeptide chain is the primary determinant of its structure. The amino acid sequence determines the type and location of secondary structures. Additionally, the overall tertiary structure of a protein is predominantly stabilized by chemical bonds between amino acid side chains&#8212;the unique chemical groups that distinguish amino acids from each other. These side chains are either charged (positively or negatively), polar-uncharged, or non-polar.
The amino acids have unique physical and chemical characteristics depending on their side-chain groups. For example, polar and charged amino acids interact with water to form hydrogen bonds and are called hydrophilic. In contrast, the non-polar amino acids avoid interactions with water and are called hydrophobic. Hence when a protein is folded in a cellular environment, side chains of hydrophobic amino acids are buried in the core of the protein away from the aqueous surroundings. In contrast, the hydrophilic amino acid side chains are exposed on the protein&#39;s surface.
The tightly packed hydrophobic amino acids in the protein core lead to the formation of weak Van der Waals interactions between the side chain groups. These Van der Waals forces impart added stability to the folded protein. The polar amino acids exposed on the protein&#39;s surface are free to form hydrogen bonds with water molecules or other polar amino acid side chains. The positively and negatively charged amino acids are also present on a protein&#39;s exterior, where they form ionic bonds with other nearby, oppositely charged amino acids.
Disulfide bonds form between two sulfhydryls, or SH, groups on the amino acid cysteine. This is a robust interaction that acts like reinforcement on the folded protein. Disulfide bonds lock the folded protein in its most favored three-dimensional conformation. Proper folding of a protein also depends on other factors of the cellular environment like pH, salt concentration, temperature, etc. Alteration of the physical and chemical conditions in a protein environment affects the chemical interactions holding the protein together and can cause the protein to misfold or unfold and lose its biological function&#8212;a process known as protein denaturation.

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

Education

JoVE Core

Cell Biology

Unit 1

Protein Structure

KEY TERMS AND CONCEPTS

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...

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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Cell Structure

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Globular and Fibrous Proteins

Translation

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protein-complexes-with-interchangeable-parts

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Structural Protein Function

Protein Networks

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HS-LS1-2

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HS-LS1-3

How Amino Acid Sequence Shapes Proteins

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