This chapter explores the structures of proteins in more detail than thus far in this text. Building on the basic structural and physical chemistry of amino acids and protein conformations, it examines the features that stabilize native states. Proteins combine the unity of a common and repetitive mainchain with the variety available from a sequence of sidechains individual to each protein. The sequence of sidechains both determines the three-dimensional structure of the protein (including its overall folding pattern in general and the structure of the active site in particular), and provides the chemistry required for function. The twenty standard amino acids contain groups of several physicochemical types and are adequate for many but not all purposes. In addition to amino acids, many proteins bind prosthetic groups—ions or small organic molecules—that stabilize or modify the structure, and/or participate in catalysis. They also serve regulatory purposes.
Chapter
Protein structure
Chapter
Setting The Stage
This chapter surveys the properties of proteins. The fundamental features of individual proteins relate to the following: the way that the sequences of amino acids assembled into polypeptide chains, the three-dimensional structures into which they fold, and the functions they perform. Proteins are created through going through the stages of Francis Crick's Central Dogma which involve the regions of the genome. They are then transcribed to RNA and translated by ribosomes to the amino-acid sequences of proteins. Next, they fold spontaneously to native structures. This is the point where life makes the leap from the one-dimensional world of DNA, RNA, and amino-acid sequences, to three-dimensions. The chapter then identifies the variety of functions that proteins provide, including structural components of cells and tissues, and the catalytic activities of enzymes. Regulation of protein expression and activity—to a large extent, by proteins—is essential in organizing the activities of cells. Finally, the chapter looks at the two main mechanisms of protein evolution, which include mutations at individual sites that allow local exploration of sequence space, and the ‘mixing and matching’ of different domains. Conversely, mutations that lead to protein dysfunction are the cause of many diseases.
Book
Nicholas C. Price and Jacqueline Nairn
Exploring Proteins is composed of three sections. The first section looks at the basic concepts and tools. In particular, the key mathematical tools. Section B considers goals and methods and includes an examination of the important properties of proteins and how to explore them. The final section discusses data analysis and looks at data analysis in practice. It considers analytical methods, purification of proteins, the protein structure, enzyme activity, the binding of ligands to proteins, and how to report experimental work.
Chapter
The important properties of proteins and how to explore them
This chapter describes the goals and methods employed to separate, identify, and characterize proteins. It begins by considering how to establish the function and structure of a protein and how its activity may be regulated. The chapter then outlines the range of assays used to monitor the biological activity of proteins; such assays underpin protein characterization and purification. The classical approach to studying proteins requires their purification from their native source using bespoke purification procedures for individual proteins. This task has been simplified greatly with the advent of protein expression in recombinant systems. The chapter then looks at how a protein is regulated within the cellular environment and the types of interactions in which it is involved. Typically, this is achieved by monitoring the effects of a number of physical and chemical variables on protein activity. Finally, the chapter discusses the use of bioinformatics in exploring the properties of proteins.
Chapter
Protein modification and targeting
This chapter reviews protein modification and targeting. Protein chaperones assist in the proper folding and unfolding of proteins by interacting with hydrophobic regions of the protein. Some proteins require the formation of disulfide bonds for their correct folding. Meanwhile, proteins are targeted to specific subcellular locations by amino acid sorting motifs, as well as by the attachment of lipids such as fatty acyl groups, isoprenoid groups, or GPI (glycosylphosphatidylinositol) anchors. The chapter then looks at post-translational cleavage. Some proteins need to be cleaved by site-specific proteases before they are active, while other proteins contain self-excising inteins, which must be removed from the protein product for it to become active. The chapter also considers covalent modification of proteins, including lipid modifications, before assessing protein degradation.
Chapter
Protein Structure
This chapter discusses the basic chemistry of proteins and illustrates some of the salient features of their three-dimensional structures. The principles of construction and design of proteins start with amino acids and builds up to complete structures. Amino acids form peptide bonds, to create a polymer chain. Each amino acid within a polypeptide chain contains a sidechain. The sequences of sidechains—dictated primarily by the DNA sequences of the genes—determine the three-dimensional structures and, thereby, the functions of proteins. In addition to the polypeptide chain, many proteins may contain atomic ions, have small organic molecules, or undergo covalent post-translational modifications. The chapter then looks at protein folding and denaturation. Most proteins form native states, folding into a compact three-dimensional structure dictated by the amino-acid sequence. In contrast, the denatured state arises when conditions of temperature or solvent break up the native state. Finally, the chapter considers protein structures, protein families, and protein interactions.
Chapter
Nitrogen metabolism: amino acid metabolism
This chapter refers to amino acids which are supplied in the diet from protein hydrolysis in the gut. This includes proteins in the body that are constantly degraded and resynthesized. The chapter clarifies how the body can synthesize about ten of the amino acids. The rest must be obtained from the diet, but all 20 are needed for protein synthesis. Amino acids are also used to synthesize a wide variety of other molecules. The chapter discusses amino acids in excess of immediate requirements and shows that these are deaminated as the amino nitrogen is mainly converted into urea in mammals and excreted. The carbon-hydrogen skeletons are oxidized to release energy or converted into fat or glycogen according to the metabolic controls operating at the time and the particular amino acid.
Chapter
Protein Synthesis
This chapter considers proteins as the most dynamic, numerous, and varied class of biomolecules, where in the uniqueness of each cell type is caused almost entirely by the proteins it produces. It is not surprising, therefore, that a relatively large amount of cellular energy is used in protein synthesis. The chapter describes the synthesis of proteins as a regulated process which is the result of their strategic importance in the cellular economy. It then turns to protein synthesis, which is the process in which genetic information encoded in the nucleic acids is translated into the 20 standard amino acid alphabet of polypeptides. In addition to translation, protein synthesis includes the processes of posttranslational modification and targeting.
Chapter
Modifications to Proteins That Control Cell Signalling
This chapter explores why post-translational modifications (PTMs) of proteins are important and analyses the action and consequences of phosphorylation. It cites examples of cell signalling that involve phosphorylation and demonstrates the role of other modifications of proteins and their ramifications for protein function. It also discusses the importance of proteins in cells, as they may have a structural role as keratin and collagen or catalytic roles that involve metabolism. The chapter outlines the levels of control that are available to cells in order to ensure that the levels of actions of proteins are appropriate. It points out how cells can control the rates of expression of the genes that encode proteins.
Chapter
Protein Synthesis, Processing, and Regulation
This chapter discusses proteins, which are the active players in most cell processes which
implement the myriad tasks that are directed by the information encoded in genomic DNA. The
chapter considers protein synthesis as the final stage of gene expression. It also describes
the polypeptide chain that must fold into the appropriate three-dimensional conformation
once synthesized and undergo various processing steps before being converted to its active
form. The chapter shows how gene expression is controlled at the level of transcription and
at the level of translation, which is an important element of gene regulation. It mentions
how proteins once synthesized can be regulated in response to extracellular signals either
by covalent modifications or by association with other molecules.
Chapter
Protein Evolution
This chapter focuses on protein evolution, which proceeds through generation of variation by mutations in DNA—gene frequencies in populations can change either by selection of favourable variants, or non-selective drift. There are two components of protein evolution. The first is divergence of amino-acid sequences within domains. ‘Mixing and matching’ of different combinations of domains is another important mechanism of divergence of protein structure and function. Gene duplication also facilitates divergence, as one copy can continue to provide an essential function while the other can develop a novel function. In addition to changes in amino-acid sequences of individual proteins, important differences between species depend on changes in regulation, either at the protein level or in control of transcription. The chapter then looks at directed evolution and computational protein design.
Chapter
Protein structure determination
This chapter discusses protein structure determinations, which involve experimental and computational methods, and combined applications of both. For many years, X-ray crystallography and fibre diffraction were the only methods for determining the positions of individual atoms in macromolecular structures. A companion appeared in the 1980s, when K. Wüthrich, R.R. Ernst, and their coworkers developed methods for solving protein structures by nuclear magnetic resonance (NMR) spectroscopy. With a third technique, cryo-electron microscopy (cryo-EM), it has been possible to determine structures of large aggregates, including viral capsids, large protein complexes, and intact ribosomes. Cryo-EM of large multiprotein complexes plus X-ray crystal structures of individual components has proved a powerful combination. The chapter also considers protein structure prediction and modelling.
Chapter
Proteins and Proteomes
This chapter focuses on the structure, features, and function of proteins. It cites amino acids as the building blocks of proteins. Proteins carry a range of functions, such as the agents of biochemical reactions of cellular metabolism or hormones transmitting signals from one cell to another. The chapter then details the four levels of protein structure that are dependent on polypeptide chains. Enzymes function as biological catalysts that make a chemical reaction more likely to occur and speed up the overall rate. The chapter acknowledges how modern protein technology methods allow the rapid identification of proteins and the growth of proteomics as a field of study.
Chapter
Proteins and Proteomes
This chapter focuses on the structure, features, and function of proteins. It cites amino acids as the building blocks of proteins. Proteins carry a range of functions, such as the agents of biochemical reactions of cellular metabolism or hormones transmitting signals from one cell to another. The chapter then details the four levels of protein structure that are dependent on polypeptide chains. Enzymes function as biological catalysts that make a chemical reaction more likely to occur and speed up the overall rate. The chapter acknowledges how modern protein technology methods allow the rapid identification of proteins and the growth of proteomics as a field of study.
Book
Arthur Lesk
Protein Science introduces the essential topics in protein science by describing the basic chemical structure of proteins, the factors that stabilize protein structures, protein function, and protein evolution. It begins by placing proteins in their general context in life. They are synthesized as amino-acid sequences encoded in genomes, and fold spontaneously to three-dimensional structures. This is the point where life makes the tremendous leap from the one-dimensional world of genome and amino-acid sequences, to the three-dimensional world of protein structures—indeed, the world which we inhabit.
Chapter
Protein Processing and Sorting:
The Endoplasmic Reticulum, Golgi Apparatus, and Lysosomes
This chapter discusses the distinction of the endoplasmic reticulum (ER), Golgi apparatus,
and lysosomes from other cytoplasmic organelles by their common involvement in protein
processing and connection by vesicular transport. It assesses tail-anchored proteins, which
are inserted into the ER membrane posttranslationally by distinct mechanisms. It also
examines the mechanisms that mediate entry and sorting of proteins into the endoplasmic
reticulum. The chapter demonstrates how protein folding is facilitated in the ER and the
mechanisms that are triggered by protein misfolding. It looks at the types of protein
glycosylation that take place in the Golgi and points out the role of the Golgi in synthesis
of membrane lipids.
Book
Arthur M. Lesk
Introduction to Protein Science firstly outlines the topics ahead. The first main topic is protein structure and protein structure determination. The next subject the text considers is bioinformatics of protein sequence and structure. Proteins as catalysts is examined after that. This discussion particularly looks at enzyme structure, kinetics, and mechanisms. The text then moves on to describe proteins with partners, the evolution of protein structure and function, and protein folding and design. Finally, it looks at proteomics and systems biology.
Chapter
Conceptual toolkit: the molecular principles for understanding proteins
This chapter discusses the principles for understanding the structures and functions of proteins. It begins by reviewing the properties of amino acids, which represent the building blocks of proteins. The chapter looks at the structure of proteins on four levels. The primary structure refers to the sequence of amino acids in the polypeptide chain, i.e. the covalent structure of the protein. The secondary structure refers to the local folding of the polypeptide chain, such that segments of the chain may form helices, strands of sheet, or turns. Meanwhile, the tertiary structure refers to the long-range folding of the polypeptide chain so that portions of the chain that are remote in terms of sequence are brought close together in space. The quaternary structure refers to the association of the individual polypeptide chains in a multi-subunit protein. The chapter then considers the forces contributing to the structures and interactions of proteins.
Chapter
Evolution of protein structure and function
This chapter looks at the evolution of protein structure and function. Protein evolution is characterized by the exploration by a set of genomes of the space of amino acid sequences in search of selectively advantageous variants. Evolution acts at the level of protein functions, in a feedback cycle that selects gene sequences. Two or more proteins are homologous if they are descended from a common ancestor. The chapter then distinguishes between two types of homologues: orthologues and paralogues. Orthologues are homologous proteins in different species, descended from a single ancestral protein, while paralogues are homologues in the same species arising from gene duplication, and their descendants. The chapter also looks at evolutionary variations in protein families, including globins, NAD-binding domains, serine proteases, and opsins. Finally, it explores how proteins can develop new functions during evolution: the mechanisms, pathways, and limitations.
Chapter
Protein
Colleen S. Deane, Daniel J. Wilkinson, and Philip J. Atherton
This chapter is concerned with proteins, the fundamental structures of life. They exist as functional elements within every cell and undergo extensive metabolic interaction. This widespread metabolic interaction is intimately linked to the metabolism of energy and other nutrients. At the most basic level, proteins are made from a combination of 20 different amino acids, which determines the structure and function. Dietary protein and exercise are the two key stimuli that promote positive protein turnover, which can be accurately and reliably measured using stable isotope methods. The potency of the anabolic response to dietary protein is dependent upon the protein quality, which can be measured via the Digestible Indispensable Amino Acid Score, Protein Digestibility Corrected Amino Acid Score, and/or using stable isotope tracers. In situations of protein deficiency, significant body mass can be lost, drastically impairing health and quality of life, requiring dietary protein therapy to help overcome/manage these conditions.
