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

В недавно синтезированном пептиде взаимодействие между составляющими его аминокислотами направляет его сворачивание в стабильную трехмерную структуру, называемую нативной конформацией, часто его функциональной формой.
Во-первых, линейная полипептидная цепь сворачивается в альфа-спирали и бета-листы посредством водородных связей между аминокислотными остатками.
Гидрофобные боковые цепи, выступающие из спиралей или бета-листов, собираются вместе, удаляя окружающие молекулы воды. В результате полипептид упаковывается в слабо свернутый промежуточный продукт с гидрофобным ядром.
Полярные остатки на поверхности создают дополнительные водородные связи и ионные взаимодействия, в то время как соседние цистеины образуют ковалентные дисульфидные связи для стабилизации белка в его нативной конформации.
Для белков с несколькими цистеинами фермент протеиндисульфидизомераза катализирует быстрый обмен тиоловых групп, обеспечивая правильное образование дисульфидных связей.
Большинство белков не сворачиваются сами по себе, и им помогают белки теплового шока и шаперонины.
Эти молекулярные шапероны ускоряют процесс сворачивания, связывая развернутый пептид и предотвращая агрегацию или создавая микросреду, в которой пептид может сворачиваться в свою нативную конформацию.

<ol>
	<li>Лодиш, Харви и др. Молекулярная клеточная биология. 8-е изд. W.H. Freeman and Company, 2016. С. 81-85</li>
	<li>Дональд Воет и Джудит Г. Воет Биохимия. 4-е изд. JOHN WILEY & SONS, INC. 2011. С. 278-290</li>
	<li>Нельсон и Кокс, Ленингер, Принципы биохимии, 7-е изд. W.H. Freeman and Company, 2016. С. 396-407</li>
</ol>

Сворачивание белка (фолдинг)

Белки представляют собой цепочки аминокислот, соединенных между собой пептидными связями. При синтезе белок сворачивается в трехмерную конформацию, необходимую для его биологической функции. Взаимодействия между составляющими его аминокислотами управляют сворачиванием белка, и, следовательно, структура белка, в первую очередь зависит от его аминокислотной последовательности. Структура белка имеет решающее значение для его биологической функции Белки выполняют широкий спектр биологических функций, таких как катализация химических реакций, обеспечение иммунологической защиты, хранение, транспорт, клеточная связь, движение и структурная поддержка. Функция белка в основном зависит от распознавания и связывания других молекул, аналогично замку и ключу. Следовательно, специфическая активность каждого белка зависит от его уникальной трехмерной архитектуры. Чтобы белок был функциональным, он должен аккуратно сворачиваться. Большинство белков проходят через несколько промежуточных форм, прежде чем свернуться в наиболее стабильную, биологически активную структуру. Неправильное сворачивание белка может ухудшить общее функционирование клетки. Накопление неправильно свернутых или развернутых белков у человека приводит к муковисцидозу, болезням Альцгеймера, Паркинсона, боковому амиотрофическому склерозу и болезни Крейтцфельдта-Якоба. Критические детерминанты структуры белка Белки состоят из одной или нескольких цепей аминокислот, называемых полипептидами. Полипептид синтезируется в виде линейной цепи, которая быстро сворачивается, образуя трехмерную структуру. Термины «полипептид» и «белок» иногда используются как взаимозаменяемые, но чаще всего белком называют свернутый полипептид, который может выполнять биологическую функцию. Структуру белка обычно описывают на четырех уровнях: первичном, вторичном, третичном и четвертичном. Большинство полипептидов складываются в компактную глобулярную третичную структуру, такую как гемоглобин, белок крови, переносящий кислород. Некоторые белки, такие как кератины, образуют длинные волокна и обычно встречаются в волосах и ногтях. Глобулярные белки растворимы в воде, в отличие от волокнистых белков. Последовательность аминокислот в полипептидной цепи является основным фактором, определяющим ее структуру. Аминокислотная последовательность определяет тип и расположение вторичных структур. Кроме того, общая третичная структура белка преимущественно стабилизируется за счет химических связей между боковыми цепями аминокислот — уникальными химическими группами, которые отличают аминокислоты друг от друга. Эти боковые цепи либо заряжены (положительно или отрицательно), либо полярно-незаряжены, либо неполярны. Аминокислоты обладают уникальными физическими и химическими характеристиками в зависимости от групп их боковой цепи. Например, полярные и заряженные аминокислоты взаимодействуют с водой с образованием водородных связей и называются гидрофильными. Напротив, неполярные аминокислоты избегают взаимодействия с водой и называются гидрофобными. Следовательно, когда белок сворачивается в клеточной среде, боковые цепи гидрофобных аминокислот спрятаны в ядре белка вдали от водного окружения. Напротив, боковые цепи гидрофильных аминокислот обнажены на поверхности белка. Плотно упакованные гидрофобные аминокислоты в ядре белка приводят к образованию слабых ван-дер-ваальсовых взаимодействий между группами боковых цепей. Эти силы Ван-дер-Ваальса придают свернутому белку дополнительную стабильность. Полярные аминокислоты, находящиеся на поверхности белка, могут образовывать водородные связи с молекулами воды или боковыми цепями других полярных аминокислот. Положительно и отрицательно заряженные аминокислоты также присутствуют на внешней стороне белка, где они образуют ионные связи с другими близлежащими противоположно заряженными аминокислотами. Дисульфидные связи образуются между двумя сульфгидрильными или SH-группами аминокислоты цистеина. Это надежное взаимодействие, которое действует как усиление свернутого белка. Дисульфидные связи фиксируют свернутый белок в его наиболее предпочтительной трехмерной конформации. Правильное сворачивание белка также зависит от других факторов клеточной среды, таких как pH, концентрация соли, температура и т. д. Изменение физических и химических условий в окружающей среде белка влияет на химические взаимодействия, удерживающие белок в его структурном состоянии, и может вызвать его неправильное сворачивание или разворачивание, что приводит к утрате его биологической функции — этот процесс известен как денатурация белка.

Белки представляют собой цепочки аминокислот, соединенных между собой пептидными связями. При синтезе белок сворачивается в трехмерную конформацию, критически важную для ...

Education

JoVE Core

Cell Biology

Клеточная биология

Unit 1

Раздел 1

Protein Structure

Структура белка

KEY TERMS AND CONCEPTS

ОСНОВНЫЕ ТЕРМИНЫ И ПОНЯТИЯ

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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Visualizing Onion and Cheek Cells
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Cell Diversity

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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

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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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structural-organization-of-the-human-body-an-overview

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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

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

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Oogenesis

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What is a Sensory System?

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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

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What Are Osmoregulation and Excretion?

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Blood Withdrawal I

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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

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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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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?

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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 ...

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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