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

在新合成的多肽中，其组成氨基酸之间的相互作用引导多肽折叠形成稳定的三维结构，称为天然构象，这通常是其发挥功能的形式。
首先，线性多肽链通过氨基酸残基之间的氢键作用折叠形成α-螺旋和β-折叠结构。
从螺旋或β-折叠突出的疏水性侧链相互聚集，排除周围的水分子。因此，多肽链折叠形成具有疏水核心的松散折叠中间体。
表面的极性残基可形成额外的氢键和离子相互作用，而相邻的半胱氨酸则形成共价二硫键，以稳定蛋白质的天然构象。
对于含有多个半胱氨酸的蛋白质，蛋白质二硫键异构酶可催化巯基基团的快速交换，从而促进正确二硫键的形成。
大多数蛋白质无法自行折叠，需要热休克蛋白和伴侣素的帮助。
这些分子伴侣通过结合未折叠的多肽，防止其发生聚集，或提供一个微环境，使多肽能够折叠成其天然构象，从而加速折叠过程。

<ol>
	<li>Lodish， Harvey 等人，分子细胞生物学。第 8 版，WH Freeman and Company，2016 年。第 81-85 页</li>
	<li>Donald Voet和Judith G Voet生物化学。 第4版。 JOHN WILEY & SONS， INC. 2011。第 278-290 页</li>
	<li>Nelson 和 Cox， Lehninger，《生物化学原理》，第 7 版，W.H. Freeman and Company，2016 年。第 396-407 页</li>
</ol>

蛋白质折叠

蛋白质是由氨基酸通过肽键连接而成的链状结构。合成后，蛋白质折叠成三维构象，这对其生物学功能至关重要。蛋白质折叠受到其组成氨基酸之间相互作用的引导，因此蛋白质结构主要取决于其氨基酸序列。

蛋白质结构对其生物学功能至关重要

蛋白质具有广泛的生物功能，例如催化化学反应、提供免疫防御、储存、运输、细胞通讯、运动和结构支持。蛋白质的功能主要取决于识别和结合其他分子，类似于锁和钥匙。因此，每种蛋白质的特定活性都取决于其独特的三维结构。

蛋白质要发挥功能，必须准确折叠。大多数蛋白质在折叠成最稳定的生物活性结构之前会经历几种中间形式。蛋白质错误折叠会损害细胞的整体功能。 错误折叠或未折叠蛋白质在人体中的积累会导致囊性纤维化、阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和克雅氏病。

蛋白质结构的关键决定因素

蛋白质由一条或多条称为多肽的氨基酸链组成。多肽作为线性链合成后，会迅速折叠成三维结构。术语“多肽”和“蛋白质”有时可以互换使用，但最常见的是，能够执行生物学功能的折叠多肽称为“蛋白质”。蛋白质结构通常分为四个层次：一级、二级、三级和四级。 大多数多肽折叠成整体紧凑的球状三级结构，例如血红蛋白，血液中的携氧蛋白质。 角蛋白等一些蛋白质形成长纤维，常见于头发和指甲中。 与纤维状蛋白质不同，球状蛋白质可溶于水。

多肽链中的氨基酸序列是其结构的主要决定因素。 氨基酸序列决定二级结构的类型和位置。 此外，蛋白质的整体三级结构主要由氨基酸侧链之间的化学键稳定——这些独特的化学基团将氨基酸彼此区分开来。这些侧链要么是带电的（正电或负电）、极性不带电，要么是非极性的。

氨基酸根据其侧链基团而具有独特的物理和化学特性。 例如，极性和带电氨基酸与水相互作用形成氢键，称为亲水性的。 相反，非极性氨基酸避免与水相互作用，被称为疏水性氨基酸。 因此，当蛋白质在细胞环境中折叠时，疏水性氨基酸的侧链被埋在蛋白质的核心中，远离水环境。 相反，亲水性氨基酸侧链暴露在蛋白质表面。

蛋白质核心中紧密堆积的疏水性氨基酸导致侧链基团之间形成弱的范德华相互作用。 这些范德华力为折叠后的蛋白质增加了稳定性。暴露在蛋白质表面的极性氨基酸可以自由地与水分子或其他极性氨基酸侧链形成氢键。 带正电和负电的氨基酸也存在于蛋白质的外部，它们与附近其他带相反电荷的氨基酸形成离子键。

氨基酸半胱氨酸上的两个巯基或 SH 基团之间会形成二硫键。 这是一种强大的相互作用，起到强化折叠蛋白质的作用。二硫键将折叠的蛋白质锁定在其最有利的三维构象中。 蛋白质的正确折叠还取决于细胞环境中的其他因素，如 pH、盐浓度、温度等。蛋白质环境中物理和化学条件的改变会影响将蛋白质结合在一起的化学相互作用，并可能导致蛋白质错误折叠 或者展开并失去其生物功能——这一过程称为蛋白质变性。

蛋白质是由氨基酸通过肽键连接而成的链状分子。合成后，蛋白质会折叠成特定的三维构象，这对……至关重要。

Education

教育

JoVE Core

Cell Biology

细胞生物学

Unit 1

第一单元

Protein Structure

蛋白质结构

KEY TERMS AND CONCEPTS

关键术语与概念

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 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

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
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Cytoplasm

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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

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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

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RNA Structure

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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

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Animal and Plant Cell Structure

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Overview of Human Digestion

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Anatomy of the Intestines

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Accessory Organs

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Lipid Digestion

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Protein Digestion

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Carbohydrate Digestion

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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

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The Sympathetic Nervous System

Overview

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Oogenesis

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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

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What is the Skeletal System?

Overview

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

An Introduction to the Zebrafish: Danio rerio

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Physiology of the Circulatory System

Homeostasis
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Anatomy of the Circulatory System

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Measuring Blood Pressure
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Anatomy of the Heart

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Measuring Circulatory System Function in Humans
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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
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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
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What is the Immune System?

Overview

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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

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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?

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Negative and Positive Feedback

Homeostatic Imbalance

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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

How Amino Acid Sequence Shapes Proteins

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