When will scientists be able to take any amino acid sequence and accurately predict both that protein’s three-dimensional conformations and its chemical properties? What breakthroughs will be needed to accomplish this important goal?
Are there ways to reveal the detailed workings of a protein machine that do not require the purification of each of its component parts in large amounts, so that the machine’s functions can be reconstituted and dissected using chemical techniques in a test tube?
What are the roles of the dozens of different types of covalent modifications of proteins that have been found in addition to those listed in Table 3–3? Which ones are critical for cell function and why?
Why is amyloid toxic to cells and how does it contribute to neurodegenerative diseases such as Alzheimer’s disease?
Which statements are true? explain why or why not.
3–1 Each strand in a β sheet is a helix with two amino acids per turn.
3–2 Intrinsically disordered regions of proteins can be identified using bioinformatic methods to search genes for encoded amino acid sequences that possess high hydrophobicity and low net charge.
3–3 Loops of polypeptide that protrude from the surface of a protein often form the binding sites for other molecules.
3–4 An enzyme reaches a maximum rate at high substrate concentration because it has a fixed number of active sites where substrate binds.
3–5 Higher concentrations of enzyme give rise to a higher turnover number.
3–6 Enzymes that undergo cooperative allosteric transitions invariably consist of symmetric assemblies of multiple subunits.
3–7 Continual addition and removal of phosphates by protein kinases and protein phosphatases is wasteful of energy—since their combined action consumes ATP— but it is a necessary consequence of effective regulation by phosphorylation.
Discuss the following problems.
3–8 Consider the following statement. “To produce one molecule of each possible kind of polypeptide chain, 300 amino acids in length, would require more atoms than exist in the universe.” Given the size of the universe, do you suppose this statement could possibly be correct? Since counting atoms is a tricky business, consider the problem from the standpoint of mass. The mass of the observable universe is estimated to be about 1080 grams, give or take an order of magnitude or so. Assuming that the average One such kelch repeat domain is shown in Figure Q3–1. Would you classify this domain as an “in-line” or “plug-in” type domain?
˜7 Figure Q3–1 The kelch repeat domain of
D. dendroides (Problem 3–10). The seven individual β propellers are color coded and labeled. The Nand C-termini are indicated by N and C.
3–11 Titin, which has a molecular weight of about 3 × 106, is the largest polypeptide yet described. Titin molecules extend from muscle thick filaments to the Z disc; they are thought to act as springs to keep the thick filaments centered in the sarcomere. Titin is composed of a large number of repeated immunoglobulin (Ig) sequences of 89 amino acids, each of which is folded into a domain about 4 nm in length (Figure Q3–2A).
You suspect that the springlike behavior of titin is caused by the sequential unfolding (and refolding) of individual Ig domains. You test this hypothesis using the atomic force microscope, which allows you to pick up one end of a protein molecule and pull with an accurately measured force. For a fragment of titin containing seven repeats of the Ig domain, this experiment gives the sawtooth force-versus-extension curve shown in Figure Q3–2B. If the experiment is repeated in a solution of 8 M urea (a protein denaturant), the peaks disappear and the measured extension becomes much longer for a given force. If the experiment is repeated after the protein has been cross-linked by treatment with glutaraldehyde, once again the peaks disappear but the extension becomes much smaller for a given force.