Anexo: Descripción de los casos de uso del sistema

PROTEIN STRUCTURE AND FUNCTION

2009 Garland Science Publishing 3^rd Edition

The Shape and Structure of Proteins

4-1 For each of the following sentences, fill in the blanks with the best word or phrase selected from the chapter on Protein Structure and Function.

A protein is similar to a charm bracelet that has a linear linked chain or backbone with charms hanging off at regular intervals. Similar to the amino acid sequence of a protein, it is the sequence and identity of the charms that dictate the character of the bracelet. The part of a protein that is analogous to the bracelet chain is called the __________________ backbone. The parts of a protein that are analogous to the charms are called the __________________.

4-2 Which of the following statements is TRUE?

(a) Peptide bonds are the only covalent bonds that can link together two amino acids in proteins.

(b) The polypeptide backbone is free to rotate about each peptide bond.

(c) Nonpolar amino acids tend to be found in the interior of proteins.

(d) The sequence of the atoms in the polypeptide backbone varies between different proteins.

(e) A protein chain ends in a free amino group at the C-terminus.

4-3 For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once.

A newly synthesized protein generally folds up into a

__________________ conformation. All the information required to determine a protein’s conformation is contained in its amino acid __________________. On heating, a protein molecule will become __________________ due to breakage of __________________ bonds.

On removal of urea, an unfolded protein can become

__________________. The final folded conformation adopted by a protein is that of __________________ energy.

composition irreversible reversible

covalent lowest sequence

denatured noncovalent stable

highest renatured unstable

4-4 Typical folded proteins have a stability ranging from 7 to 15 kcal/mol at 37°C. Stability is a measure of the equilibrium between the folded (F) and unfolded (U) forms of the protein, with the unfolded form having a greater free energy. See Figure Q4-4. For a protein with a stability of 7.1 kcal/mol, calculate the fraction of protein that would be unfolded at equilibrium at 37°C. The equilibrium constant (K_eq) is related to the free energy (∆G°) by the equation: K_eq = 10^{–∆G°/1.42}

Figure Q4-4

4-5 You wish to produce a human enzyme, protein A, by introducing its gene into bacteria.

The genetically engineered bacteria make large amounts of protein A, but it is in the form of an insoluble aggregate with no enzymatic activity. Which of the following procedures might help you to obtain soluble, enzymatically active protein? Explain your reasoning.

A. Make the bacteria synthesize protein A at a slower rate and in smaller amounts.

B. Dissolve the protein aggregate in urea, then dilute the solution and gradually remove the urea.

C. Treat the insoluble aggregate with a protease.

D. Make the bacteria overproduce chaperone proteins in addition to protein A.

E. Heat the protein aggregate to denature all proteins, then cool the mixture.

4-6 Which of the following statements about proteins is TRUE?

(a) The three-dimensional structure of a protein can usually be predicted from knowledge of its amino acid sequence.

(b) Two proteins having similar amino acid sequences will often have similar shapes.

(c) Proteins containing fewer than 100 amino acids cannot fold into stable structures.

(d) Most proteins contain more than 2000 amino acids.

(e) The detailed three-dimensional structure of a protein can usually be determined by electron microscopy.

4-7 The α helix and β sheet are found in many different proteins because they are formed by (a) hydrogen bonding between the amino acid side chains most commonly found in

proteins.

(b) noncovalent interactions between amino acid side chains and the polypeptide backbone.

(c) ionic interactions between charged amino acid side chains.

(d) hydrogen bonding between atoms of the polypeptide backbone.

(e) hydrophobic interactions between the many nonpolar amino acids.

4-8 A. In the schematic diagram of a protein given in Figure Q4-8, label the three protein strands that are linked together in a β sheet with a “b”.

Figure Q4-8 B. Is this β sheet parallel or antiparallel?

4-9 For each polypeptide sequence listed, choose from the options given below to indicate which secondary structure the sequence is most likely to form upon folding. The nonpolar amino acids are italicized.

A. Leu-gly-val-leu-ser-leu-phe-ser-gly-leu-met-trp-phe-phe-trp-ile B. Leu-leu-gln-ser-ile-ala-ser-val-leu-gln-ser-leu-leu-cys-ala-ile C. Thr-leu-asn-ile-ser-phe-gln-met-glu-leu-asp-val-ser-ile-arg-trp

amphipathic α helix hydrophilic α helix hydrophobic α helix amphipathic β sheet hydrophilic β sheet

4-10 A helical structure

(a) will contain two, three, four, or some other exact number of subunits per each turn of the helix.

(b) that is right-handed if viewed from one end will appear to be left-handed if viewed from its other end.

(c) can form only by joining together a string of identical protein molecules.

(d) can form either within a single large molecule or from an assembly of separate molecules.

(e) is usually maintained entirely by covalent bonds.

4-11 Drawn below are segments of β sheets, which are rigid pleated structures held together by hydrogen bonds between the peptide backbones of adjacent strands (Figure Q4-11).

The amino acid side chains attached to the C_α carbons are omitted for clarity.

Figure Q4-11

A. Indicate whether each structure is parallel or antiparallel.

B. Draw the hydrogen bonds as dashed lines (- - - -).

4-12 For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once.

The α helices and β sheets are examples of protein __________________

structure. A protein such as hemoglobin, which is composed of more than one protein __________________, has __________________ structure.

A protein’s amino acid sequence is known as its __________________

structure. A protein __________________ is the modular unit from which many larger single-chain proteins are constructed. The three-dimensional conformation of a protein is its __________________ structure.

allosteric ligand secondary

domain primary subunit

helix quaternary tertiary

4-13 You are digesting a protein 625 amino acids long with the enzymes Factor Xa and thrombin, which are proteases that bind to and cut proteins at particular short sequences of amino acids. You know the amino acid sequence of the protein and so can draw a map of where factor Xa and thrombin should cut it (Figure Q4-13). You find, however, that treatment with each of these proteases for an hour results in only partial digestion of the protein, as summarized under the figure. List the segments (A–E) of the protein that are most likely to be folded into compact, stable domains.

Figure Q4-13

4-14 Calculate how many different amino acid sequences there are for a polypeptide chain 10 amino acids long.

4-15 All known proteins in cells adopt a single stable conformation because

(a) any chain of amino acids can fold up into only one stable conformation.

(b) protein chains that can adopt several different conformations have been weeded out by natural selection.

(c) chaperone proteins prevent the protein from adopting a preferred unstable conformation.

(d) they are complexed with other molecules that keep them in that one particular conformation.

(e) one conformation always has the most positive free energy.

4-16 A friend tells you that she has just discovered that the protein responsible for causing dogs to chase cars is a member of the MAP protein kinase family. In response to your blank stare, she adds that the yeast protein Fus3p, which is involved in response to a yeast hormone is also a MAP kinase family member. Although you still have no idea of what either a MAP kinase or Fus3p is, which one or more of the following statement(s) can you safely predict to be TRUE? Explain your reasoning.

(a) The dog protein and Fus3p have mostly similar amino acid sequences.

(b) The dog protein and Fus3p catalyze the transfer of a phosphate group to another molecule.

(c) The dog protein phosphorylates the same type of molecule that Fus3p phosphorylates.

(d) The dog protein and Fus3p have identical three-dimensional structures.

(e) The dog protein is involved in response to hormones.

4-17 A hemoglobin molecule

(a) is composed of four protein domains.

(b) is a dimer of polypeptide chains.

(c) has two binding sites for nitrogen gas.

(d) is composed of two different types of protein subunits.

(e) is composed of four identical protein subunits.

4-18 When purified samples of protein Y and a mutant version of protein Y are both washed through the same gel-filtration column, mutant protein Y runs through the column much slower than the normal protein. Which one or more of the following changes in the mutant protein is/are most likely to explain this result?

(a) The loss of a binding site on the mutant protein surface through which protein Y normally forms dimers

(b) A change that results in the mutant protein acquiring an overall positive instead of a negative charge

(c) A change that results in mutant protein Y being larger than the normal protein (d) A change that results in mutant protein Y having a slightly different shape from

the normal protein

(e) The loss of a binding crevice in the mutant protein Y for a small molecule ligand 4-19 Examine the three protein monomers in Figure Q4-19. From the arrangement of

complementary binding surfaces, which are indicated by similarly shaped protrusions and invaginations, decide whether each monomer could assemble into a defined multimer, a filament, or a sheet.

Figure Q4-19

4-20 For each of the following indicate whether the individual folded polypeptide chain forms a globular (G) or fibrous (F) protein molecule.

A. Keratin

(a) are formed by the cross-linking of methionine residues.

(b) are formed mainly in proteins that are retained within the cytosol.

(c) stabilize but do not change a protein’s final conformation.

(d) can be broken by oxidation through agents such as mercaptoethanol.

(e) rarely form in extracellular proteins.