ch. 4 translation and protein structure book notes

side chain:

A chemical group attached to the central carbon atom of an amino acid, whose structure and composition determine the identity of the amino acid; also known as an R group.

ribosome:

A complex structure of RNA and protein, bound to the cytosolic face of the RER in the cytoplasm, on which proteins are synthesized.

peptide bond:

A covalent bond that links the carbon atom in the carboxyl group of one amino acid to the nitrogen atom in the amino group of another amino acid.

operon:

A group of functionally related genes located in tandem along the DNA and transcribed as a single unit from one promoter; the region of DNA consisting of the promoter, the operator, and the coding sequence for the structural genes.

protein family:

A group of proteins that are structurally and functionally related.

codon:

A group of three adjacent nucleotides in RNA that specifies an amino acid in a protein or that terminates polypeptide synthesis.

polypeptide:

A polymer of amino acids connected by peptide bonds.

initiation factor:

A protein that binds to mRNA to initiate translation.

elongation factor:

A protein that breaks the high-energy bonds of the molecule GTP to provide energy for ribosome movement and elongation of a growing polypeptide chain.

release factor:

A protein that causes a finished polypeptide chain to be freed from the ribosome. The release factor causes the bond connecting the polypeptide to the tRNA to break, creating the carboxyl terminus of the polypeptide and completing the chain. Once the finished polypeptide is released, the small and large ribosomal subunits disassociate from the mRNA and from each other.

chaperone:

A protein that helps shield a slow-folding protein until it can attain its proper three-dimensional structure. binds with hydrophobic groups and nonpolar R groups to shield them from inappropriate aggregation, and in repeated cycles of binding and release they give the polypeptide time to find its correct shape.

folding domain:

A region of a protein that folds in a similar way across a protein family relatively independently of the rest of the protein.

aminoacyl tRNA synthetase:

An enzyme that attaches a specific amino acid to a specific tRNA molecule. attach specific amino acids to tRNAs and are therefore responsible for translating the codon sequence in an mRNA into an amino acid sequence in a protein.

the actual translation of each codon in the mRNA into one amino acid in the polypeptide is carried out by means of transfer RNA (tRNA).

Each tRNA has the nucleotide sequence CCA at its 3′ end, and the 3′ hydroxyl of the A is the attachment site for the amino acid corresponding to the anticodon

structure of amino acid:

It consists of a central carbon atom, called the α (alpha) carbon, connected by covalent bonds to four different chemical groups: an amino group (-NH2), a carboxyl group (-COOH), a hydrogen atom (-H), and a variable side chain or R group.

Explain the relationship between protein folding and protein function.

In many cases, the ability of a protein to perform its function is dependent upon the protein being in the correct conformation. For example, many enzymes bind to their substrate through specific interactions between their active sites and a site on the substrate. If a mutation causes an amino acid change in the gene resulting in the enzyme having a different shape or different chemical property (e.g., negatively charged instead of polar), it may no longer be able to bind to its substrate and perform its activity.

termination:

In protein translation, the time at which the addition of amino acids stops and the completed polypeptide chain is released from the ribosome. In cell communication, the stopping of a signal.

alpha (α) helix:

One of the two principal types of secondary structure found in proteins. the polypeptide backbone is twisted tightly in a right-handed coil with 3.6 amino acids per complete turn. The helix is stabilized by hydrogen bonds that form between each amino acid's carbonyl group (C=O) and the amide group (N-H) four amino acids ahead in the sequence. the chemical properties of the projecting R groups largely determine where the α helix is positioned in the folded protein

The codon at which translation begins is called the _________ codon, and it is coded by AUG, which specifies Met (amino acid methionine)

initiation

β (beta) sheet:

One of the two principal types of secondary structure found in proteins. the polypeptide folds back and forth on itself, forming a pleated sheet that is stabilized by hydrogen bonds between carbonyl groups in one chain and amide groups in the other chain across the way. The R groups project alternately above and below the plane of the β sheet. β sheets typically consist of 4 to 10 polypeptide chains aligned side by side, with the amides in each chain hydrogen-bonded to the carbonyls on either side (except for those at the ends of each strand). the polypeptide chains are said to be antiparallel but β sheets can also be formed by hydrogen bonding between polypeptide chains that are parallel (pointing in the same direction). However, the antiparallel configuration is more stable because the carbonyl and amide groups are more favorably aligned for hydrogen bonding.

aminoacyl (A) site:

One of three binding sites for tRNA on the large subunit of a ribosome.

exit (E) site:

One of three binding sites for tRNA on the large subunit of a ribosome.

peptidyl (P) site:

One of three binding sites for tRNA on the large subunit of a ribosome.

translation:

Synthesis of a polypeptide chain corresponding to the coding sequence present in a molecule of messenger RNA. (added amino acids)

messenger RNA (mRNA):

The RNA molecule that combines with a ribosome to direct protein synthesis; it carries the genetic "message" from the DNA to the ribosome.

Explain how the order of amino acids determines the way in which a protein folds.

The order of amino acids in the polypeptide chain determines the way in which proteins fold because of the various interactions and bonds formed between the amino acids. These interactions, depending on the type and location, will give rise to a specific secondary and tertiary structure. More often than not, these structures must be perfectly arranged for the protein to function. Thus, it is important that the polypeptide chain be correctly ordered to result in the specific structure of that particular protein.

initiation:

The stage of translation in which methionine is established as the first amino acid in a new polypeptide chain, after an initiator AUG codon is recognized

secondary structure:

The structure formed by interactions between stretches of amino acids in a protein. nearby amino acid interactions

quaternary structure:

The structure that results from the interactions of several polypeptide chains, polypeptide subunits. the polypeptide subunits may be identical or different & the subunits can influence each other in subtle ways and influence their function

denaturation:

The unfolding of proteins by chemical treatment or high temperature that disrupts the hydrogen and ionic bonds holding the tertiary structure together; the separation of paired, complementary strands of nucleid acid. proteins lose their functional activity

Name four major groups of amino acids, categorized by the properties of their R groups. Explain how the chemical properties of each group affect protein shape.

Amino acids can be categorized into five main groups based on the properties of their side chains: The first are the hydrophobic amino acids, "water-fearing," whose side chains are nonpolar, usually found buried in the interior of the folded proteins, and typically form bonds with other hydrophobic amino acids or solvents (e.g., valine). In the second group are the hydrophilic amino acids, "water-loving," that have polar side chains, usually found on the outside surface of folded proteins, and typically form bonds with other hydrophilic amino acids or water. Their charge allows them to interact with other proteins and macromolecules. Hydrophilic amino acids are also broken up into two groups: basic amino acids with side chains that are positively charged at intracellular pH (e.g., lysine) and acidic amino acids with side chains that are negatively charged (e.g., aspartic acid). The fifth group are "special" amino acids, whose unique structures and chemical properties have significant effects on higher levels of protein structure because they allow more or less flexibility around the peptide bond (glycine and proline), or covalent interactions between side chains (cysteine).

carboxyl group:

COOH; a carbon atom with a double bond to oxygen and a single bond to a hydroxyl group.

reading frame:

Following a start codon, a consecutive sequence of codons for amino acids. The different ways of parsing the string into three-letter words. the ribosome establishes the correct reading frame for the codons

amino acids: glycine, proline & cysteine

Glycine is different from the other amino acids because its R group is hydrogen, exactly like the hydrogen on the other side of the α carbon, and therefore it is not asymmetric. All of the other amino acids have four different groups attached to the α carbon and are asymmetric. In addition, glycine is nonpolar and small enough to tuck into spaces where other R groups would not fit. glycine increases the flexibility of the polypeptide backbone, which can be important in the folding of the protein. Proline is also distinctive, but for a different reason. Note how its R group is linked back to the amino group. This linkage creates a kink or bend in the polypeptide chain and restricts rotation of the C-N bond, thereby imposing constraints on protein folding in its vicinity, an effect the very opposite of glycine's. Cysteine makes a special contribution to protein folding through its -SH group. When two cysteine side chains in the same or different polypeptides come into proximity, they can react to form an S-S disulfide bond, which covalently joins the side chains. Such disulfide bonds are stronger than the ionic interactions of other pairs of amino acid, and form cross-bridges that can connect different parts of the same protein or even different proteins.

amino group:

NH2; a nitrogen atom bonded to two hydrogen atoms, covalently linked to the central carbon atom of an amino acid.

alpha (α) carbon:

The central carbon atom of each amino acid.

Describe the relationship between the template strand of DNA, the codons in mRNA, anticodons in tRNA, and amino acids.

The codons of mRNA are groups of three nucleotides that code for a particular amino acid. Each is transcribed from the template strand of DNA according to the normal rules of base pairing (but in RNA, U replaces T). The sequence of the codons in the mRNA gives rise to the order of the resulting amino acid polypeptide chain. The codons are translated by tRNAs. The sequence of each tRNA includes a group of three nucleotides called an anticodon that is complementary in sequence and thus can recognize and bind to a specific codon in the mRNA. Because of the complementary and antiparallel nature of nucleic acid structures, an anticodon in a tRNA has the same 3' to 5' sequence as the template DNA, except with U's instead of T's. Each tRNA is also bound to a specific amino acid, affiliated with a particular anticodon/codon pair, on the 3' end of the molecule. When the mRNA is being "read" through the ribosome, the order of the amino acids in the polypeptide chain is dependent upon the sequential interaction of the mRNA codon with the correct tRNA anticodon/amino acid pair.

genetic code:

The correspondence between codons and amino acids, in which 20 amino acids are specified by 64 codons.

amino end:

The end of a polypeptide chain that has a free amino group.

carboxyl end:

The end of a polypeptide chain that has a free carboxyl group.

proteins:

The key structural and functional molecules that do the work of the cell, providing structural support and catalyzing chemical reactions. The term "protein" is often used as a synonym for "polypeptide."

tertiary structure:

The overall three-dimensional shape of a protein (polypeptide), formed by long-range interactions between secondary structures. determined by the spatial distribution of hydrophilic and hydrophobic R groups along the molecule, as well as by different types of chemical bonds and interactions (ionic, hydrogen, and van der Waals) that form between various R groups. the tertiary structure usually includes loops or turns in the backbone that allow these R groups to sit near each other in space and for bonds to form. The primary structure determines the secondary and tertiary structures. Furthermore, tertiary structure determines function because it is the three-dimensional shape of the molecule—the contours and distribution of charges on the outside of the molecule and the presence of pockets that might bind with smaller molecules on the inside—that enables the protein to serve as structural support, membrane channel, enzyme, or signaling molecule.

elongation:

The process in protein translation in which successive amino acids are added one by one to the growing polypeptide chain.

A mutation leads to a change in one amino acid in a protein. The result is that the protein no longer functions properly. How is this possible?

The sequence of amino acids in a protein determines how a protein folds, so a change in even a single amino acid can affect the way the protein folds and can disrupt its function. For example, if the hydrophobic R groups of two amino acids must aggregate for proper structure and function, then a mutation that changes one of the hydrophobic amino acids for an acidic or a basic amino acid will prevent this aggregation and disrupt structure and function. Similarly, if proper folding requires interaction between the R groups of an acidic and a basic amino acid, then, if either one of them is changed to a hydrophobic amino acid, proper folding will not take place.

primary structure:

The sequence of amino acids in a protein.

anticodon:

The sequence of three nucleotides in a tRNA molecule that base pairs with the corresponding codon in an mRNA molecule.

Describe how peptide bonds, hydrogen bonds, ionic bonds, disulfide bridges, and noncovalent interactions (van der Waals forces and the hydrophobic effect) define a protein's four levels of structure.

The way in which amino acids interact and bond in a polypeptide chain is important for the structure and function of the protein. Peptide bonds are important in maintaining the primary structure of a polypeptide chain. These bonds form between the carboxyl group of one amino acid and the amino group of the next amino acid in the chain. Note that these bonds are typically found between amino acid residues in the polypeptide. Hydrogen bonds are important in maintaining the secondary structure of the polypeptide chain. These bonds form between the oxygen in the carbonyl group (C=O) of one peptide bond and the hydrogen in the amide group (NH) of another. This allows regions of the polypeptide to interact with itself and fold. Two common types of secondary structure formed by hydrogen bonding are α helices and β sheets. Note that in terms of secondary structure, these bonds are found between groups in the polypeptide backbone. There are four groups of bonds or interactions important in creating tertiary and quaternary structure. The first group is the ionic bonds that form between a negative charge and a positive charge. For example, an ionic bond would form between a basic amino acid and an acidic amino acid because they have oppositely charged side chains. These bonds can occur between amino acids that are far apart in the polypeptide chain, thus creating loops and bends in the overall structure. The second group is the hydrogen bonds that form between the oxygen of one amino acid's side chain and the hydrogen of another amino acid's side chain. The third group is the disulfide bridges. These covalent bonds form between two cysteine residues in the same polypeptide chain, or between two cysteines in two different chains. Note that when discussing tertiary structure, these bonds are found between different side chains. The fourth group important to maintaining tertiary and quaternary structure is noncovalent interactions that include van der Waals forces and hydrophobic interactions that maintain interactions with different domains of the protein and result in a protein's specific shape.

Describe the steps of translation initiation, elongation, and termination.

Translation of mRNA by ribosomes can be divided into three processes: Initiation:Initiation factors bind to the 5' cap of the mRNA (in eukaryotic cells) or at the Shine‒Dalgarno sequence (for prokaryotes), and recruit the small subunit of the ribosome and a tRNA charged with methionine. This complex then moves along the mRNA until it finds a start codon (AUG, coding for methionine). The large ribosomal subunit then joins the complex and causes the initiation factors to be released. The tRNAMet is then bound in the P site of the ribosome. The next tRNA, determined by the codon of the mRNA, binds in the A site of the ribosome. This elicits a coupled reaction in which the bond between the Met and its tRNA is broken and a new bond is formed between the carboxyl group of the Met and the amino group of the next amino acid (a peptide bond). The ribosome complex then slides to the next codon on the mRNA, shifting the now uncharged tRNAMet to the E site, where it is released from the ribosome complex, and the peptide-bearing tRNA to the P site. The A site is now free for the next charged tRNA. Elongation:The ribosome continues in this fashion, shifting down the mRNA one codon at a time, adding amino acids to the growing peptide chain. Elongation factors provide the energy needed for these reactions to happen. Termination:When the ribosome complex comes across a stop codon (UAA, UAG, or UGA), a protein release factor binds in the A site of the ribosome and causes the bond between the polypeptide chain and the last tRNA to break. Once the polypeptide chain is released, the ribosomal subunits disassociate from the mRNA and each other and translation is complete.

Name and describe two ways that proteins can acquire new functions in the course of evolution.

Two ways in which proteins can acquire new functions through the course of evolution are (1) mutation and selection and (2) combining different folding domains. (1) Mutation and selection: The sequence of the amino acids in the polypeptide chain is important for the proper folding, and ultimately the function, of the protein. If the sequence is altered by a mutation that changes a codon to specify for a different amino acid, this could affect the function of the protein and whether it is selected for in the population. A mutation that leads to a nonfunctioning protein will most likely lead to the impaired survival and reproductive ability of that organism and will thus be eventually eliminated from the population. A neutral mutation that does not impair or improve protein function will likely remain in the population because those organisms will survive and reproduce at normal levels. A mutation that improves the function of the protein, although rare, would give a selective advantage to that organism if it could survive and reproduce more successfully. (2) Combining different folding domains: Form leads to function. If a gene gains a new folding domain by joining with a folding domain from another gene, for example, its product now has the additional function provided by that folding domain. If this function is beneficial or benign to the protein and ultimately to the survival and reproductive ability of the organism, the new gene, and therefore protein, will be maintained in the population.

4.3 Proteins evolve through mutation and selection and by combining functional units.

• A protein family is a group of proteins that are structurally and functionally related. • There are far fewer protein families than the total number of possible proteins because the probability that a random sequence of amino acids will fold properly to carry out a specific function is very small. • A region of a protein that folds in a particular way and that carries out a specific function is called a folding domain. • Proteins evolve by combining different folding domains. page • Proteins also evolve by changes in amino acid sequence, which occurs by mutation and selection.

4.1 Proteins are linear polymers of amino acids that form three-dimensional structures with specific functions.

• An amino acid consists of an α carbon connected by covalent bonds to an amino group, a carboxyl group, a hydrogen atom, and a side chain or R group. • There are 20 common amino acids that differ in their R groups. Amino acids are categorized by the chemical properties of their R groups—hydrophobic, basic, acidic, polar—and by special structures. • Amino acids are connected by peptide bonds to form proteins. • The primary structure of a protein is its amino acid sequence. The primary structure determines how a protein folds, which in turn determines how it functions. • The secondary structure of a protein results from the interactions of nearby amino acids. Examples include the α helix and β sheet. • The tertiary structure of a protein is its three-dimensional shape, which results from long-range interactions of amino acid R groups. • Some proteins are made up of several polypeptide subunits; this group of subunits is the protein's quaternary structure. • Chaperones help some proteins fold properly.

4.2 Translation is the process by which the sequence of bases in messenger RNA specifies the order of successive amino acids in a newly synthesized protein.

• Translation requires many cellular components, including ribosomes, tRNAs, and proteins. • Ribosomes are composed of a small and a large subunit, each consisting of RNA and protein; the large subunit contains three tRNA-binding sites that play different roles in translation. • An mRNA transcript of a gene has three possible reading frames composed of three-nucleotide codons. • tRNAs have an anticodon that base pairs with the codon in the mRNA and carries a specific amino acid. • Aminoacyl tRNA synthetases attach specific amino acids to tRNAs. • The genetic code defines the relationship between the three-letter codons of nucleic acids and their corresponding amino acids. It was deciphered using synthetic RNA molecules. • The genetic code is redundant in that many amino acids are specified by more than one codon. • Translation consists of three steps: initiation, elongation, and termination.