Textbook of Structural Biology

Anders Liljas, Lars Liljas;Miriam-Rose Ash;G?ran Lindblom;Poul Nissen;Morten Kjeldgaard

• Publisher: WSPC
• Year: 2016
• ISBN:
  9789813142497
• Edition: 2
• Topic: Ciencias biológicas
• Subtopic: Bioquímica

-->

This book provides a comprehensive coverage of the basic principles of structural biology, as well as an up-to-date summary of some main directions of research in the field. The relationship between structure and function is described in detail for soluble proteins, membrane proteins, membranes, and nucleic acids.

There are several books covering protein structure and function, but none that give a complete picture, including nucleic acids, lipids, membranes and carbohydrates, all being of central importance in structural biology.

The book covers state-of-the-art research in various areas. It is unique for its breadth of coverage by experts in the fields. The book is richly illustrated with more than 400 color figures to highlight the wide range of structures.

-->

Request Inspection Copy

--> Contents: Introduction;Basics of Protein Structure;The Folding, Folds and Functions of Proteins;Basics of Membrane Proteins;Basics of Nucleic Acid Structure;Basics of Lipids and Membrane Structure;Basics of Carbohydrates;Enzymes;Genome Structure, DNA Replication and Recombination;Transcription;Protein Synthesis — Translation;Protein Folding and Degradation;Transmembrane Transport;Signal Transduction;Cell Motility and Transport;Structural Aspects of Cell-Cell Interactions;The Immune System;Virus Structure and Function;Bioinformatics Tools in Structural Biology; --> -->
Readership: Undergraduate and graduate students in structural biology, chemistry, biochemistry, biology and medicine. -->
Proteins, Enzymes, Nucleic Acids, Lipids, Membranes, Membrane Proteins, Carbohydrates, Structure and Function, Replication, Transcription, Translation, Folding and Degradation, Signaling, Motility and Transport, Cell-Cell Interaction, The Immune System, Viruses and Bioinformatics Tools

• The book covers research in the separate areas
• The breadth of the coverage by experts in the fields
• The book is rich in color illustrations to highlight the wide range of structures

1

Introduction

1.1Life

We are surrounded by microbes, plants and animals that we immediately recognize as living beings (Figure 1.1). However, it is still difficult to provide a concise definition what life is. Perhaps the most useful definition for this book is that life is a unit capable of chemical activities, which can reproduce and evolve.

Chemical activities, which involve conversions of energy and matter, are called metabolism. These activities capture energy and chemical matter in different forms. Thousands of chemical activities take place simultaneously in a living organism and they must be well coordinated or regulated to maintain the stability of the living unit.

Reproduction of the unit (generating new units) provides both the continuity and the variation that is also an important characteristic of life. The combination of reproduction, horizontal transfer of information and “erroneous” duplicates provides the basis of evolution. In other words, the composition of the unit should be able to change over time to better adapt to the changing environmental conditions. Living organisms appear in very different forms and follow very different life-styles. However, the basic characteristics of life (including metabolism, reproduction and evolution) are provided and governed by very similar sub-structures: biological macromolecules and cells.

1.2Levels of Organization of Life

The living world has several hierarchical levels, ordered from the smallest to the largest. At the bottom are molecules, a mix of inorganic and organic compounds and biological macromolecules, followed by sub-cellular structures, cells, tissues, organs, organisms, populations, communities and the biosphere, which encompasses all biological communities on the Earth.

Fig. 1.1 ▪ Living organisms are found in numerous different forms. Left: A microscope picture of baker’s yeast (Saccharomyces cerevisiae) cells (by the courtesy of Concetta Compagno). Right: Linneas (Linnea borealis) covering vast areas of Lapland (by the courtesy of Bernarda Rotar) and bottom: moose, the largest land animals in Scandinavia (by the courtesy of Aca.Pixus.dk). Within these different macro-forms very similar molecular structures can be found, which determine the form and lifestyle of the carrier organisms.

Macromolecules are central in all living organisms. They are giant polymers consisting of repeating units. These repeating units may or may not be identical, and are connected with covalent or non-covalent bonds. Macromolecules perform a multitude of functions, which are the basis of metabolism, reproduction and evolution, such as energy or information storage, reaction catalysis, coordination and regulation, communication, structural support, defense, movement and transport. On the basis of chemical composition we talk about three different kinds of macromolecules: (i) peptides and proteins that are polymers of amino acid residues, (ii) nucleic acids, which are polymers of nucleotides, and (iii) carbohydrates, which are polymers of sugars (Figure 1.2). Other central molecules that should be mentioned here are the lipids. Although they are not macromolecules, they self-assemble into large aggregates of macromolecular dimensions, including the lipid bilayer (an important building block of cell membranes), micellar aggregates containing bile molecules, and the aggregates of lipoproteins that transport cholesterol and fat in the blood stream. In the following chapters we will try to understand the structures of bio-macromolecules and link them to their functions and the higher levels of the living world.

Fig. 1.2 ▪ A simplified picture of two bio-macromolecules, which are the focus of our further chapters. Left: The structure of a well-known protein, chymotrypsin (PDB: 4CHA). Right: A nucleic acid molecule, yeast tRNAPhe (PDB: 1EHZ).

The basic unit of life is a cell (Figure 1.3). Cells are surrounded by a plasma membrane, which separates each cell from the external environment and creates a segregated compartment with a controlled internal environment. Cells show two organizational patterns: (i) prokaryotic, characteristic for Bacteria and Archaea, and (ii) eukaryotic, characteristic for Eukarya. Prokaryotic cells usually exist as single cells and are smaller than eukaryotic ones, typically on the order of 1 μm in diameter. The basic structure of a prokaryotic cell is defined by a cellular membrane, an intracellular nucleoid containing DNA, and the cytosol holding the rest of the intracellular material, where ribosomes, enzymes and cytoskeletal elements are found. Eukaryotic cells are usually at least ten times larger than prokaryotic cells and more complex, with inner membranes separating compartments and organelles. The organelles include: (i) the nucleus, storing genetic material and the replication and gene transcription systems (ii) the cytosol, where protein synthesis and many essential biochemical reactions take place, (iii) the mitochondrion, a power plant and energy storage compartment, (iv) the endoplasmatic reticulum and Golgi apparatus, where proteins are matured and sorted to further locations, (v) the lysosomes or vacuoles, where polymeric macromolecules, such as proteins, are recycled into usable metabolites.

Fig. 1.3 ▪ A schematic picture of an animal cell showing sub-cellular structures, such as nucleus, membrane systems (ER), mitochondrion, etc. (Made by Michael W. Davidson, Florida State University.)

All organisms on Earth seem to originate from a single unicellular organism. The main reasons why one can claim that all organisms originate from the same cell is that not only do all living species use the same nucleotides and amino acids despite many other possibilities, but the genetic code (the dictionary for translation from the language of nucleic acids to the one of proteins) is the same. In addition, central molecular systems like transcription and translation are strongly related. A smaller molecule like ATP is the universal currency of energy in all living organisms, although in principle many other choices would have been possible.

Today, many millions of different organisms that do not interbreed with each other are found and we call them species (Figure 1.4). They are all adapted to their different environments and in a naive sense they may seem perfect. However, a particular life form may not be fit tomorrow and thereby become extinct, like so many other species in the past, which have previously populated Earth. Due to changes of environment, new and better-fit species constantly evolve over time, and this evolution works by gradually changing the structures of macromolecules.

The unfolding of events leading to the present diversity is expressed as an evolutionary tree showing the order in which species split and evolved into new species. This tree traces the descendants coming from ancestors that lived at different times in the past.

Fig. 1.4 ▪ A simplified tree of life. The common progenitor originated approximately 4 billion years ago. The position of the first branchings, occurring between the progenitor of Bacteria, Archaea and Eukarya, are still unclear.

In other words, the evolutionary tree shows the evolutionary relationship among modern and ancient species. It is important to understand the evolutionary relationship between organisms when one compares the structure of macromolecules from these organisms, being involved in similar processes. Some of the earlier branching is difficult to reconstruct because there are no available fossils. However, based on molecular evidence in modern organisms, we can separate all living organisms into three domains, which have been evolving separately for more than 1 billion years: (i) Archaea, (ii) Bacteria, and (iii) Eukarya. Even if they superficially look similar, Archaea and Bacteria separated into distinct lineages very early during evolutionary history.

Archaea are often inhabitants of extreme environments, such as hot and acidic springs, sea depths and salt brines, but can also be found in more “normal” environments. Their replication, transcription and translation machinery resembles the eukaryotic machinery, while their metabolism and energy conversion resemble the bacterial ones.

Bacteria consist of more than a dozen sub-groups, also called clades, but the most important are: Protobacteria, Cyanobacteria, Spirochetes, Chlamydias and Firmicutes. The Protobacteria are the largest and a very diverse group, including one of the beststudied organisms, Escherichia coli. Sometimes bacteria are divided, on the basis of their cell wall composition, into gram-positive, including Bacillus subtilis, and gram-negative, including E. coli. Bacteria exhibit the greatest biochemical diversity.

Eukarya can be divided into four groups: Protista, Plantae, Fungi and Animalia. The Protista contain mostly single celled organisms and have a polyphyletic origin, meaning that some represent very primitive eukaryotes, such as Giardia, while some are closely related to animals, such as Dictyostelium, or plants, such as red algae. Phagotrophy, a feeding mode to form a pocket in the plasma membrane and enclose the “food”, is a hallmark of Eukarya.

1.3Short History of Life on Earth

The theory of chemical evolution holds that conditions on the primitive Earth, around 4 billion years ago, led to the emergence of the first biological molecules. Oparin and Haldane independently suggested in the 1920s that if Earth’s first atmosphere was reducing, and if there was a supply of external energy then a range of organic compounds might be synthesized. In the 1950s, Stanley Miller and Harold Urey mimicked these conditions in the lab. Water vapor, hydrogen gas, ammonia and methane gas were exposed to sparks, and after a few days the system contained several complex molecules, such as amino acids and nucleic acid bases, the building blocks of today’s life. When the monomeric units were present, it was not so difficult to achieve polymerization even under abiotic conditions. However, how could the first peptides and nucleic acids become “alive”? In other words, how could they start reproducing and evolving?

The term replicator means a structure that can arise only if there is a preexisting structure of the same kind in the vicinity. For example, a supersaturated solution crystallizes if a small seeding crystal is added. However, this represents a simple replicator relying on a single structure. More sophisticated replicators could exist in several forms and thereby could have contributed to heredity. For sustained evolution, an indefinite number of forms and indefinite variation in heredity is necessary. The first artificial replicator, a simple hexadeoxynucleotide not needing enzymes for its replication (polymerization from the present mono-units) was synthesized by von Kiedrowski in 1986. The first short RNA molecules may have had the ability to catalyze the polymerization of offspring molecules. The first replicating RNA molecules competed successfully with their own erroneous copies and with other less-efficient systems for the monomers needed for their replication. Even if self-replicating RNA molecules fulfill the above criteria for life, the path to the first cells was still more sophisticated. One of the main following steps was to include peptides and proteins to establish the RNA — protein world, followed by the introduction of membrane systems, thereby segregating the primitive cell from its environment.

The origin of the first cell, the common progenitor of all living organisms, could be approximately 3.5 billion years ago, and at that time simple replication and translation machineries already existed. One hypothesis suggests that, during the following 2 billion years, the unicellular system evolved to represent a fine net of metabolic reactions connected to increasingly sophisticated machineries for nucleic acid replication and RNA to protein translation, also keeping plasticity, enabling the cell to respond to the demands of the ever-changing environment. During this period, the first living cells were still dependent on organic compounds, which were the primary source of energy, and had abiotic origin. Later, approximately 2.5 billion years ago, one of the major steps was the evolution of the ability to use the energy of sunlight to power metabolism. Photosynthesis provided energetic independence and soon resulted in vast quantities of organic materials and oxygen. The evolution of aerobic metabolism significantly changed cellular biochemistry. Many enzymatic reactions became dependent, directly or indirectly, on the presence of oxygen. Aerobic metabolism allowed cells to grow larger. Some of the further major transitions include the origin of sex, the origin of multicellular organisms and the origin of social groups. Behind all these events stood proteins, nucleic acids, carbohydrates and lipids, with their evolving structures and functions.

1.4What is Structural Biology and When Did It Start?

The field of structural biology focuses on a classical insight: in order to understand, we need to see. “Seeing is believing”, or “a picture says more than a thousand words” are well-known phrases. This is true whether we deal with large objects, as in astronomy and astrophysics, medium-sized objects such as birds or fishes, or with very small objects like biochemical systems or particle physics. Structural biology is the science that tries to make the sub-cellular and molecular objects of biolo...