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

新たに合成されたペプチドでは、その構成アミノ酸間の相互作用により、天然の立体配座と呼ばれる安定した三次元構造(多くの場合、その機能形態)に折り畳まれます。
まず、直鎖状のポリペプチド鎖は、アミノ酸残基間の水素結合を通じてα-ヘリックスとβ-シートに折り畳まれます。
ヘリックスまたはベータシートから突き出た疎水性の側鎖が一緒になり、周囲の水分子が除去されます。その結果、ポリペプチドは、疎水性コアを有する緩く折り畳まれた中間体に詰め込まれます。
表面上の極性残基は追加の水素結合とイオン相互作用を作り、隣接するシステインは共有ジスルフィド結合を形成してタンパク質の天然構造を安定化させます。
複数のシステインを持つタンパク質の場合、タンパク質ジスルフィドイソメラーゼ酵素はチオール基の迅速な交換を触媒し、正しいジスルフィド結合形成を可能にします。
ほとんどのタンパク質はそれ自体で折りたたまれず、熱ショックタンパク質とシャペロニンによって助けられます。
これらの分子シャペロンは、折り畳まれていないペプチドに結合して凝集を防ぎ、ペプチドが本来のコンフォメーションに折り畳まれる微小環境を提供することにより、フォールディングプロセスをスピードアップします。

<ol>
	<li>Lodish, Harvey, et al. Molecular Cell Biology. 第8版 W.H. Freeman and Company, 2016.81-85ページ</li>
	<li>Donald Voet and Judith G Voet Biochemistry. 第4版、JOHN WILEY & SONS, INC. 2011.278-290ページ</li>
	<li>ネルソンとコックス、レーニンガー、生化学の原則、第7版WHフリーマンアンドカンパニー、2016年。396-407ページ</li>
</ol>

タンパク質のフォールディング

タンパク質は、ペプチド結合によって結合されたアミノ酸の鎖です。 タンパク質は合成されると、その生物学的機能にとって重要な三次元立体構造に折り畳まれます。 構成アミノ酸間の相互作用はタンパク質の折り畳みをガイドするため、タンパク質の構造は主にそのアミノ酸配列に依存します。

タンパク質の構造はその生物学的機能にとって重要です

タンパク質は、化学反応の触媒、免疫学的防御、貯蔵、輸送、細胞通信、運動、および構造的支持の提供など、幅広い生物学的機能を実行します。 タンパク質の機能は主に、鍵と錠前に似た他の分子の認識と結合に依存しています。 したがって、各タンパク質の比活性は、その独自の三次元構造に依存します。

タンパク質が機能するためには、正確に折りたたまれなければなりません。 ほとんどのタンパク質は、最も安定した生物学的に活性な構造に折りたたまれる前に、いくつかの中間形態を経ます。 タンパク質のミスフォールディングは、細胞の全体的な機能を損なう可能性があります。 ヒトにおけるミスフォールドまたはアンフォールディングタンパク質の蓄積は、嚢胞性線維症、アルツハイマー病、パーキンソン病、筋萎縮性側索硬化症、およびクロイツフェルト・ヤコブ病を引き起こします。

タンパク質構造の重要な決定因子

タンパク質は、ポリペプチドと呼ばれる 1 つ以上のアミノ酸の鎖で構成されています。 ポリペプチドは直鎖として合成され、それ自体が急速に折り畳まれて三次元構造を形成します。 ポリペプチドとタンパク質という用語は、同じ意味で使用されることもありますが、最も一般的には、生物学的機能を実行できる折り畳まれたポリペプチドがタンパク質と呼ばれます。 タンパク質の構造は通常、一次、二次、三次、四次の 4 つのレベルで記述されます。 ほとんどのポリペプチドは、血液中の酸素を運ぶタンパク質であるヘモグロビンのように、全体的にコンパクトな球状の三次構造に折りたたまれます。 ケラチンなどの一部のタンパク質は長い繊維を形成し、髪や爪によく見られます。 球状タンパク質は、繊維状タンパク質とは異なり、水に可溶です。

ポリペプチド鎖内のアミノ酸の配列は、その構造の主な決定因子です。 アミノ酸配列は二次構造の種類と位置を決定します。 さらに、タンパク質の全体的な三次構造は、主にアミノ酸側鎖間の化学結合によって安定化されます。アミノ酸側鎖は、アミノ酸を互いに区別する固有の化学基です。 これらの側鎖は、帯電 (正または負)、極性、非帯電、または無極性のいずれかです。

アミノ酸は、側鎖グループに応じて独特の物理的および化学的特性を持っています。 たとえば、極性の荷電アミノ酸は水と相互作用して水素結合を形成し、親水性と呼ばれます。 対照的に、非極性アミノ酸は水との相互作用を回避し、疎水性と呼ばれます。 したがって、タンパク質が細胞環境で折りたたまれると、疎水性アミノ酸の側鎖が水性環境から離れたタンパク質のコアに埋め込まれます。 対照的に、親水性アミノ酸側鎖はタンパク質の表面に露出しています。

タンパク質コア内に密に詰まった疎水性アミノ酸により、側鎖グループ間に弱いファンデルワールス相互作用が形成されます。 これらのファンデルワールス力は、折りたたまれたタンパク質にさらなる安定性を与えます。 タンパク質の表面に露出した極性アミノ酸は、水分子または他の極性アミノ酸側鎖と自由に水素結合を形成します。 正および負に荷電したアミノ酸はタンパク質の外側にも存在し、そこで近くにある他の反対に荷電したアミノ酸とイオン結合を形成します。

ジスルフィド結合は、アミノ酸システイン上の 2 つのスルフヒドリル (SH) 基の間に形成されます。 これは、折りたたまれたタンパク質を強化するように作用する強力な相互作用です。 ジスルフィド結合は、折りたたまれたタンパク質を最も好ましい三次元立体構造に固定します。 タンパク質の適切なフォールディングは、pH、塩濃度、温度などの細胞環境の他の要因にも依存します。タンパク質環境における物理的および化学的条件の変化は、タンパク質を結合している化学的相互作用に影響を与え、タンパク質の誤ったフォールディングを引き起こす可能性があります。 または、展開して生物学的機能を失います。これはタンパク質変性として知られるプロセスです。

タンパク質は、ペプチド結合によって結合されたアミノ酸の鎖です。合成時に、タンパク質は三次元の立体配座に折り畳まれます。

Education

JoVE Core

Cell Biology

細胞生物学

Unit 1

ユニット1

Protein Structure

タンパク質構造

KEY TERMS AND CONCEPTS

主要用語と概念

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 細胞生物学は、複雑な細胞プロセスを、わかりやすく包括的なアニメーション ビデオ レッスンで説明します。このコレクションは、細胞小器官や膜、細胞輸送、細胞のエネルギー学など、細胞の必須コンポーネントと機能に焦点を当てています。これは、実際の研究実験における細胞生物学の応用を実証する科学者による実際のビデオによって補足されています。

new-york-state-science-learning-standards

New York State Science Learning Standards

Structure and Function

HS-LS1-1.

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
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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

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

Protein Complexes with Interchangeable Parts

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.]

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

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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

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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

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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

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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 ...

Positive and Negative Feedback Loops

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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

How Amino Acid Sequence Shapes Proteins

Description

Transcript

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