Summary molecular biology of the cell, exam 1, chapter 2-8 PDF

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Molecular Biology of the Cell-Test 1Chapter 1Chapter 2Four types of noncovalent attractions help bring molecules together in cellsElectrostatic attractions (ionic bonds) hydrogen bonds , Van der Waals attractions and hydrophobic forces are 4 types of noncovalent attractions that together are effecti...

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Molecular Biology of the Cell-Test 1 Chapter 1 Chapter 2 Four types of noncovalent attractions help bring molecules together in cells Electrostatic attractions (ionic bonds) hydrogen bonds, Van der Waals attractions and hydrophobic forces are 4 types of noncovalent attractions that together are effective to face thermal motions and keep together 2 separate (macro)molecules. Noncovalent compared to covalent bonds are weaker in water, yet this only involves the electrostatic attractions and the hydrogen bonds. Hydrogen bonds are based on a special type of polar attraction, an electropositive hydrogen atom is shared by 2 electronegative atoms. The hydrogen atom can be seen as a proton that has partially dissociated from a donor atom and is now shared by a second acceptor. This bond, unlike typical electrostatic interaction, is highly directional and at best when a straight line can be drawn between the 3 involved atoms. Hydrophobic force isn’t really a bond, the force is caused by pushing nonpolar surfaces out of the hydrogen-bonded water network where they would otherwise interfere with the highly favorable interactions between water molecules. By bringing 2 nonpolar surfaces together to reduce their contact with water, the force is nonspecific. Yet hydrophobic forces are important to the proper folding of proteins.

Some polar molecules form acids and bases in water A proton (H+) causes the forming of a hydronium ion (H3O+) when a polar molecule is surrounded by water and the hydrogen charged nucleus/proton is attracted to the partial negative charge of the O-atom of the H2O molecule. The reverse reaction also takes place very readily. Substances that release protons when dissolved in water and form H3O+ are called acids. And the higher the concentration of H3O, the more acidic the solution. This concentration is expressed using a logarithmic scale, called the pH scale. (Ranging from 7,0 basic) Strong acids lose their protons easily, weak acids hold on its protons more tightly when dissolved in water. Many of the acids important in the cell are weak acids. Because protons can be passed easily to many types of molecules in cells, the concentration of H3O+ inside a cell must be regulated. Acids (especially weak ones) will give up their protons easier if the H3O+ concentration is low, and vice versa. Any molecule able to accept a proton from a water molecule is called a base. In living cells there are a lot of weak bases, those have a weak tendency to accept a proton from water. Since the reaction of H3O+ with OH- results in 2 water molecules, its logical that an increase of concentration of OH- results in a decrease in concentration in H3O+. A pure solution of water includes equal parts of both (pH 7,0). The interior of a cell is also kept close to neutral by a buffer, weak acids and bases that can release or take up protons near pH 7, keeping the environment of the cell constant under variable conditions.

A cell is formed from carbon compounds Nearly all molecules in a cell are based on carbon (excluding H2O and potassium). Carbon is an element able to form large molecules, having 4 places to form a covalent bond and having highly stable C-C bonds to form chains and rings to create large and complex molecules without limit. The carbon compounds made by cells are called organic molecules, all other molecules are inorganic. Certain combinations of atoms occur repeatedly in the molecules made by cells. Each such chemical group has distinct chemical and physical properties that influence the behavior of the molecule.

Cells contain four major families of small organic molecules Some small organic molecules of the cell, made up from up to 30 carbon atoms, are used as a monomer subunit to construct giant polymeric macromolecules, (proteins, nucleic acids and polysaccharides, so NO fatty acids!) others are energy sources, broken down into small molecules in an intercellular metabolic pathway, and some are both. Next to that, small molecules are much less abundant than organic macromolecules. Since organic molecules are all made of the same set of compounds, the compound of a cell is chemically related and classified in four major families: sugars, fatty acids, nucleotides and amino acids. Even though not all compounds in a cell can be classified in these groups, those 4 families of small organic molecules together with macromolecules made by linking them in large chains, account for the largest fraction of the cell mass.

The chemistry of cells is dominated by macromolecules with remarkable properties By weight macromolecules are the most abundant carbon-containing molecules in a living cell. They are the building blocks of a cell. Macromolecules are polymers that are made by linking monomers into long chains. Proteins are abundant and versatile, performing many functions. For example, enzymes, the catalysts that create and break many bonds, enzymes catalyze many reactions whereby cells extract energy from food molecules. Other proteins are used to build structural components, others act as molecular motors to produce force and movement. Although the chemical reactions for adding subunits to each polymer is different for proteins, nucleic acids and polysaccharides, they share important features. Each polymer grows by addition of a monomer onto the end of a growing chain by a condensation reaction. It’s important for the polymer chain to not be assembled at random from subunits, but in a precise sequence.

Noncovalent bonds specify both the precise shape of a macromolecule and its binding to other molecules Most of the covalent bonds in a macromolecule allow rotation of the atoms they join, this allows macromolecules to adopt an almost unlimited number of shapes, conformations, caused by thermal energy to rotate them. Yet most shapes of biological macromolecules are constrained caused by many weak noncovalent bonds that form between different parts of

the molecule. Thus, the polymer chain can prefer a specific conformation determined by the chain of monomers. Most protein and RNA molecules fold tightly in a preferred shape. Biological macromolecules can add up to create a strong attraction between 2 different molecules. This form of molecular interactions makes selection possible, since the close multipoint contacts required for strong binding make it possible for macromolecules to select out just one of the many thousands of other types of molecules present inside a cell. Furthermore, because the strength of the binding depends on the number of noncovalent bonds that are formed, interactions of almost all affinity are possible, allowing rapid dissociation where appropriate. Binding of this type underlies all biological catalysis, making it possible for proteins to function as enzymes plus noncovalent interactions allow macromolecules to be used as building blocks for the formation of larger structures.

Panel 2-3, 2-4, 2-5, 2-6 read in the book 94-101 Chapter 3 Proteins are most of the cell’s dry mass. They are building blocks, responsible for a cell’s function. E.g., proteins that are enzymes provide molecular surfaces that catalyze many chemical reactions, proteins in the plasma membrane form channels and pumps. Other proteins carry messages, act as signal integrators, or are tiny machines with moving parts (kinesin propels organelles through cytoplasm, topoisomerase untangles knotted DNA molecules). And of course, proteins that are antibodies, toxins, hormones, antifreeze molecules, elastic fibers, ropes, or sources of luminescence.

The shape of a protein is specified by its amino acid sequence A protein consists of a long unbranched chain of amino acids (20 in total), linked to each other by a covalent peptide bond. Proteins are therefor also known as polypeptides. Each protein has a unique sequence of amino acids. The polypeptide backbone is the core of the polypeptide chain. Attached to it are the 20 different amino acids side chains, those aren’t involved in making a peptide bond. Some side chains are nonpolar, hydrophobic, negatively/positively charged, easy to form covalent bonds and so on.

The requirement that no 2 atoms overlap, and other constraints limit the possible bond angles in a polypeptide chain, thus restricting the 3-dimensional conformations. Yet they still fold in many ways. The folding of a protein is also determined by many different sets of weak noncovalent bonds that form between one part of the chain and another. Individual noncovalent bonds are 30-300 times weaker than covalent bonds, but parallel together, they are very strong, this strength determines the stability of each folded shape. Also, the hydrophobic force is important in aquatic circumstances. They tend to be forced together to minimize their disruptive effect on the hydrogen-bonded network of H2Omolecules. Therefore, an important factor of folding any protein is the distribution of (non)polar amino acids. Nonpolar amino acids tend to cluster in the center of the molecule to avoid contact with H2O, polar groups tend to arrange them near the outside of a molecule where they can form hydrogen bonds.

Proteins fold into a conformation of lowest energy The final 3-dimensional conformation of a protein is the one that minimizes its free energy. By using a solvent which disrupts the noncovalent interactions holding the folded chain together, the protein denatures and loses its shape. When this solvent is removed, it renatures and goes back to its original shape. This indicate that the amino acid sequence contains all the information needed for specifying the 3-dimensional shape of a protein. Most proteins fold up in 1 stable conformation, but when interacting with other molecules, this can change. Which is crucial for protein function. Molecular chaperones often assist in protein folding. They bind to partly folded polypeptide chains and help them progress along the most energetically favorable folding way. They also prevent hydrophobic regions from associating with each other to form proteins aggregates. Large proteins usually consist of several protein domains (structural units that fold independently of each other).

The  helix and the  sheet are common folding patterns The  helix and the  sheet are 2 regular folding patterns found in almost all proteins, since it doesn’t require any specific side groups. This is because the folds are cause by hydrogenbonds between the N-H and CO groups of the polypeptide backbone. The cores of many proteins contain extensive regions of  sheet. They can either form parallel chains or antiparallel chains. Both types of  sheet produce a very rigid structure held together by hydrogen-bonds. An  helix is formed when a single polypeptide chain twists itself and forms hydrogen bonds between every 4th peptide bond, linking the N-H bond of one peptide bond to the CO bond of another. The helix twists fully every 3.6 amino acids. Regions of the  helix are usually a lot in proteins in the cell membranes. The hydrophilic polypeptide backbone is hydrogen-bonded to itself and shielded from the hydrophobic lipid environment of the membrane by its protruding nonpolar sidechains. A coiled-coil is a structure in which  helices wrap around each other. These can form when their nonpolar side chains are on one side, so they can twist with these side chains facing inward. These coiled-coil provide the structural framework for many elongated proteins.

Protein domains are modular units from which larger proteins are built There are 4 levels of organization in the structure of a protein: primary structure= the amino acid sequence, secondary structure= the stretches of polypeptide chain that form  helices and  sheets, tertiary structure= the full 3-dimensional structure and the quaternary structure= the complete structure. There is central importance of a unit of organization distinct from these 4, the protein domain, a substructure produced by any contiguous part of a polypeptide chain that can fold independently of the rest of the protein into a compact structure. A domain usually contains 40 to 350 amino acids, and it is the modular unit from which many larger proteins are made. The smallest protein molecules contain only a single domain, where larger one can contain more, connected to each other by a polypeptide chain.

Few of the many possible polypeptide chains will be useful to cells Since there are 20 amino acids, there are 20n different possible side chains n amino acids long. This can result in such a large number that is would not be possible. Thus a selection has been made by natural selection. Proteins with unpredictable and variable structure and

biochemical activity don’t help the cells survival and are eliminated. Due to evolution, the amino acid sequence of most present-day proteins have a single conformation state which is finely tuned for its chemical functions. But when one amino acid is changed, the complete structure can be disrupted and function is lost, this can be disastrous.

Proteins can be classified into many families Once a protein had evolved that folded up into a stable conformation, its structure could be modified to enable it to perform new functions. As a result, many proteins now can be grouped into protein families, each family member having an amino acid sequence and a 3dimensional conformation that resembles those of other family members. E.g., the family serine proteases, a family of protein-cleaving enzymes, each having different functions, yet amino sequences that match, just like their virtual twists and turns. In general, the protein structure has been more reserved in a family than the amino acid sequence, thus even when only 25% of the amino acid sequence match, the structure can still be the same. Usually, the structure is even necessary to determine if the proteins are family. The differences in amino acid sequence can have been because of positive side effect, but most of them are neutral, having no benefits or damaging effects on the basic structure and function of the protein. And some are even already lost by natural selection, because mutation altered the structure so bad, that they were harmed. Related genes that have resulted from a gene duplication event within a single genome are called paralogs. Genes that are related by descent, so genes in 2 separate species that derive from the same ancestral gene in the last common ancestor of those 2 species, are called orthologs.

Some protein domains are found in many different proteins In the evolutionary process called domain shuffling, many large proteins have evolved through the joining of preexisting domains in new combinations. Protein modules are a subset of domains that were especially mobile during evolution. They seem to have very versatile structures.  sheet based domains have achieved their evolutionary success because they provide a convenient framework for the generation of new binding sites for ligands, requiring only small changes to their protruding loops. Next to that, these protein domains have their N and C ends at the opposite poles of the domain, thus when the DNA encoding such a domain undergoes tandem duplication, the duplicated domains can be linked in series to form extended structures. These are especially common in extracellular matrix molecules and in the extracellular portions of the cell-surface receptor proteins. Sometimes there are “plug-in” types, when the C and N ends are together, and they form an insertion into a loop region of the second protein.

Certain pairs of domains are found together in many proteins We can construct a large table displaying domain usage for each organism whose genome sequence is known. We can also find that more than 2/3ds of all proteins consist of 2 or more domains, and that the same pairs of domains occur repeatedly in the same relative arrangement in a protein. Only about 5% of the 2-domain combinations are similarly shared, this suggests that most proteins containing 2-domain combinations arose through domain shuffling relatively late in evolution.

The human genome encodes a complex set of proteins, revealing that much remains unknown the result of sequencing has been surprising, seeming we relate to a tiny mustard weed based on our protein coding genes, yet our proteins each are on average more complicated. Domain shuffling during vertebrate evolution has given rise to many novel combinations of protein domains, which results in many more combinations of domains than the mustard weed. This variety in proteins increases the range of protein-protein interactions possible.

Larger protein molecules often contain more than one polypeptide chain Noncovalent bonds also allow proteins to bind to each other to produce larger structures in the cell. A binding site is any protein’s surface that can interact with another molecule through noncovalent bonds. If the binding site recognizes a second protein, the tight binding of 2 folded polypeptide chains at this site creates a larger protein molecule, each polypeptide chain is called a protein subunit. The simplest formation is when 2 identical polypeptide chains bind in a “head-to-head” way, forming 2 protein subunits, called a dimer, held together by the interactions between 2 identical binding sites.

Covalent cross-linkages stabilize extracellular proteins Many proteins are exposed to extracellular conditions, to maintain their shape, the polypeptide chains in such proteins are stabilized by covalent cross-linkages. This can be either between 2 amino acids in the same protein or connect different polypeptide chains in a multisubunit protein. Disulfide bonds (sulfate-sulfate) are the most common ones, they form as cells prepare newly synthesized proteins for export. Their info is catalyzed by the endoplasmic reticulum. They don’t change the shape of the protein. Yet these bonds aren’t needed in the mild environment inside the cell.

Protein molecules often serve as subunits for the assembly of large structures Many large objects in the cell are made by noncovalent assembly of separately manufactured molecules, which serve as the subunits of the final structure. Some benefits are: 1. It requires only a small amount of genetic information. 2. Both assembly and disassembly can be controlled reversible processes, because subunits associate through multiple bonds of low energy. 3. Errors in the synthesis can be easily avoided, since correction mechanisms can operate during assembly to exclude malformed subunits. Some subunits can assemble into a flat sheet of hexagonal patters, which can be bended into a tube or a hollow sphere. These can bind specific DNA or RNA in their interior to form the coats of viruses. These formations promote stability, because extra bonds can be formed between the subunits. Moreover, a relatively small change that affects each subunit individually can cause the structure to assemble or disassemble. This is dramatically seen in the capsid (protein coat) of a virus, it must have a particularly adaptable structure: it needs to make several contacts to create the sphere and it needs to change this arrangement to let the nucleic acid out for viral replication.

Assembly factors often aid the formation of complex biological structures

When a cellular structure held together by noncovalent bonds can’t self-assembly, part of the assembly info is provided by special enzymes and other proteins that perform the function of templates, serving as assembly factors that only guide construction.

Amyloid fibrils can form many proteins Amyloid fibrils are self-propagating stable  sheet aggregates. These fibrils are built from a series of identical polypeptide chains that become layered, creating a stack of  sheets, with the  strands oriented perpendicular to the fibril axis to form a cross-beta filament. In normal humans, the quality control mechanisms governing proteins gradually decline with age, sometimes allowing the forming of pathological aggregates. (protein aggregates) These however can add up in the cells interior when released and kill the cells and damage tissue. ...