2 Структура и функция белка (1160071), страница 26
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Denaturation destroys protein function, demonstrating arelationship between structure and function. Somedenatured proteins (e.g., ribonuclease) can renature spontaneously to give active protein, showing that the tertiary structure of a protein is determined by its amino acid sequence.The folding of globular proteins is believed tobegin with local formation of regions of secondarystructure, followed by interactions of these regionsand adjustments to reach the final tertiary structure. Sometimes regions of a polypeptide chain,called domains, fold up separately and can haveseparate functions. The final structure and thesteps taken to reach it are influenced by the needto bury hydrophobic amino acid side chains in theprotein interior away from water, the tendency of apolypeptide chain to twist in a right-handed sense,and the need to maximize hydrogen bonds andionic interactions. These constraints give rise tostructural patterns such as the /3a/5 fold andtwisted /3 pleated sheets.
Even at the level of tertiary structure, some common patterns are found inproteins that have no known functional relationship.Quaternary structure refers to the interactionbetween the subunits of oligomeric proteins orlarge protein assemblies. The best-studied oligomeric protein is hemoglobin.
The four subunitsof hemoglobin exhibit cooperative interactions onoxygen binding. Binding of oxygen to one subunitfacilitates oxygen binding to the next, giving rise toa sigmoid binding curve. These effects are mediated by subunit-subunit interactions and subunitconformational changes. Very large protein structures consisting of many copies of one or a few different proteins are referred to as supramolecularcomplexes. These are found in cellular skeletalstructures, muscle and other types of cellular "engines," and virus coats.Part II Structure and CatalysisGeneralAnfinsen, C.B. (1973) Principles that govern thefolding of protein chains.
Science 181, 223-230.The author reviews his classic work on ribonuclease.Cantor, C.R. & Schimmel, P.R. (1980) BiophysicalChemistry, Part I: The Conformation of BiologicalMacromolecules, W.H. Freeman and Company,New York.Kendrew, J.C. (1961) The three-dimensional structure of a protein molecule. Sci. Am. 205 (December), 96-111.Describes how the structure of myoglobin was determined and what was learned from it.Kim, P.S.
& Baldwin, R.L. (1990) Intermediates inthe folding reactions of small proteins. Annu. Rev.Biochem. 59, 631-660.Evolution of Catalytic Function. (1987) ColdSpring Harb. Symp. Quant. Biol. 52.A source of excellent articles on many topics, including protein structure, folding, and function.Koshland, D.E., Jr. (1973) Protein shape and biological control. Sci.
Am. 229 (October), 52-64.A discussion of the importance of flexibility in protein structures.Creighton, T.E. (1984) Proteins: Structures andMolecular Properties, W.H. Freeman and Company, New York.McPherson, A. (1989) Macromolecular crystals,Sci. Am., 260 (March), 62-69.Describes how macromolecules such as proteins arecrystallized.Oxender, D.L.
(ed) (1987) Protein Structure, Folding, and Design 2, UCLA Symposia on Molecularand Cellular Biology, New Series, Vol. 69, Alan R.Liss, Inc., New York.Summary papers from a major symposium on thetitle subject.Structure and Function of Proteins. (1989) TrendsBiochem. Sci. 14 (July).A special issue devoted to reviews on protein chemistry and protein structure. Includes good summaries of protein folding, protein structure prediction,and many other topics.Secondary, Tertiary, and QuaternaryStructureDickerson, R.E. & Geis, I.
(1982) Hemoglobin:Structure, Function, Evolution, and Pathology,The Benjamin/Cummings Publishing Company,Menlo Park, CA.Ingram, V.M. (1957) Gene mutations in humanhaemoglobin: the chemical difference between normaJ and sickle cell haemoglobin. Nature 180, 326—328.Discovery of the amino acid replacement in sicklecell hemoglobin (hemoglobin S).Pace, C.N.
(1990) Conformational stability of globular proteins. Trends Biochem. Sci. 15, 14—17.Perutz, M.F. (1978) Hemoglobin structure and respiratory transport. Sci. Am. 239 (December), 9 2 125.Richards, F.M. (1991) The protein folding problem.Sci. Am. 264 (January), 54-63.Richardson, J.S. (1981) The anatomy and taxonomy of protein structure. Adv. Prot. Chem. 34,167339.An outstanding summary of protein structural patterns and principles; the author originated the veryuseful "ribbon" representations of protein structurethat are used in many places in this chapter.Rothman, J.E.
(1989) Polypeptide chain bindingproteins: catalysts of protein folding and relatedprocesses in cells. Cell 59, 591-601.Shortle, D. (1989) Probing the determinants ofprotein folding and stability with amino acid substitutions. J. Biol. Chem. 264, 5315-5318.Chapter 7 The Three-Dimensional Structure of Proteins195Problems1. Properties of the Peptide Bond In x-ray studiesof crystalline peptides Linus Pauling and RobertCorey found that the C—N bond in the peptide linkis intermediate in length (0.132 nm) between a typical C—N single bond (0.149 nm) and a C=N double bond (0.127 nm). They also found that the peptide bond is planar (all four atoms attached to theC—N group are located in the same plane) andthat the two a-carbon atoms attached to the C—Nare always trans to each other (on opposite sides ofthe peptide bond):(a) What does the length of the C—N bond inthe peptide linkage indicate about its strength andits bond order, i.e., whether it is single, double, ortriple?(b) In light of your answer to part (a), provide anexplanation for the observation that such a C—Nbond is intermediate in length between a doubleand single bond.(c) What do the observations of Pauling andCorey tell us about the ease of rotation about theC—N peptide bond?2.
Early Observations on the Structure of WoolWilliam Astbury discovered that the x-ray patternof wool shows a repeating structural unit spacedabout 0.54 nm along the direction of the wool fiber.When he steamed and stretched the wool, the x-raypattern showed a new repeating structural unit ata spacing of 0.70 nm. Steaming and stretching thewool and then letting it shrink gave an x-ray pattern consistent with the original spacing of about0.54 nm. Although these observations providedimportant clues to the molecular structure of wool,Astbury was unable to interpret them at the time.Given our current understanding of the structureof wool, interpret Astbury's observations.3.
Rate of Synthesis of Hair a-Keratin In humandimensions, the growth of hair is a relatively slowprocess, occurring at a rate of 15 to 20 cm/yr. Allthis growth is concentrated at the base of the hairfiber, where a-keratin filaments are synthesizedinside living epidermal cells and assembled intoropelike structures (see Fig.
7-13). The fundamental structural element of a-keratin is the a helix,which has 3.6 amino acid residues per turn and arise of 0.56 nm per turn (see Fig. 7-6). Assumingthat the biosynthesis of a-helical keratin chains isthe rate-limiting factor in the growth of hair, calculate the rate at which peptide bonds of a-keratinchains must be synthesized (peptide bonds per second) to account for the observed yearly growth ofhair.4. The Effect of pH on the Conformations of Poly glutamate and Polylysine The unfolding of the ahelix of a polypeptide to a randomly coiled conformation is accompanied by a large decrease in aproperty called its specific rotation, a measure of asolution's capacity to rotate plane-polarized light.Polyglutamate, a polypeptide made up of onlyL-G1U residues, has the a-helical conformation atpH 3.
However, when the pH is raised to 7, there isa large decrease in the specific rotation of the solution. Similarly, polylysine (L-Lys residues) is an ahelix at pH 10, but when the pH is lowered to 7, thespecific rotation also decreases, as shown by thefollowing graph.a Helixa HelixRandomconformationRandom conformation02468pH1012 14What is the explanation for the effect of thepH changes on the conformations of poly(Glu) andpoly(Lys)? Why does the transition occur over sucha narrow range of pH?5.
The Bisulfide-Bond Content Determines theMechanical Properties of Many Proteins A number of natural proteins are very rich in disulfidePart II Structure and Catalysisbonds, and their mechanical properties (tensilestrength, viscosity, hardness, etc.) are correlatedwith the degree of disulfide bonding. For example,glutenin, a wheat protein rich in disulfide bonds, isresponsible for the cohesive and elastic characterof dough made from wheat flour. Similarly, thehard, tough nature of tortoise shell is due to theextensive disulfide bonding in its a-keratin. Whatis the molecular basis for the correlation betweendisulfide-bond content and mechanical propertiesof the protein?6.
Why Does Wool Shrink ? When wool sweaters orsocks are washed in hot water and/or dried in anelectric dryer, they shrink. From what you know ofa-keratin structure, how can you account for this?Silk, on the other hand, does not shrink under thesame conditions. Explain.7. Heat Stability of Proteins Containing DisulfideBonds Most globular proteins are denatured andlose their activity when briefly heated to 65 °C.Globular proteins that contain multiple disulfidebonds often must be heated longer at higher temperatures to denature them.
One such protein isbovine pancreatic trypsin inhibitor (BPTI), whichhas 58 amino acid residues in a single chain andcontains three disulfide bonds. On cooling a solution of denatured BPTI, the activity of the proteinis restored. Can you suggest a molecular basis forthis property?8. Bacteriorhodopsin in Purple Membrane ProteinsUnder the proper environmental conditions, thesalt-loving bacterium Halobacterium halobiumsynthesizes a membrane protein (Mr 26,000)known as bacteriorhodopsin, which is purple because it contains retinal. Molecules of this proteinaggregate into "purple patches" in the cell membrane. Bacteriorhodopsin acts as a light-activatedproton pump that provides energy for cell functions. X-ray analysis of this protein reveals that itconsists of seven parallel a-helical segments, eachof which traverses the bacterial cell membrane(thickness 4.5 nm).
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