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There is no rotation around the C-N bond.oHOI'i\llll// -c-\-c\-e/ll\-CN-C/l\OHHo-ciiHH;HProteinsare long polymerso f a m i n oa c i d sl i n k e db ypeptide bonds,and theyare alwayswritten with theN-terminustoward the left.The sequenceof this tripeptideis histidine-cysteine-valine.a m t n o -o rN-terminus\',ft'tt:( ll{t ,T h e s et w o s i n g l eb o n d sa l l o w r o t a t i o n ,s o t h a t l o n g c h a i n so fa m i n oa c i d sa r e v e r yf l e x i b l e .SIDECHAINSNONPOLARA C I D I CS I D EC H A I N Salanine(Val, or V)(Ala,or A)glutamicacid( G l u ,o r E )HOHOtillll-N-C-C-HOltl-N-C-C--N-C-C-(-llrHHCH,/\CH:(F],HCH:I('tl,I( )/ \leucine(.(Ile, or I)(Leu,or L)()HOHOlllttl-N-C-C--N-C-C-(tl ,HHCHII'('flr(.lljU N C H A R G EPDO L A RS I D EC H A I N SCH,CH.( ' fICH:proline(Phe,or F)(Pro,or P)HOHO-N-C-C-_N-C-C-,/\HCH,Hl-l\//\oNHzco)n,lln 9n,#At .
lI( a c t u a lal yni m i n oa c i d )|//\-N-C-C('ll,( H,CH?CHrCtlllll-N-C-C-/methioninedi*ffiiiffift$(Trp,or W)(Met, or M)HOHOtillil-N-C-C-Although the amide N is not chargedatneutral pH, it is polar.llH-N-C-C-tl( ll,C'H,is-cll rglycineH- cI I('tt,I('\\-'IoHThe -OH group is polar.(Cys,or C)(Gly,or G)HOHO- N - c -lcl rlllll-N-C-CllHHHCH,ISHDisulfidebondscan form betweentwo cysteinesidechainsin oroteins.--.u-q-q-aH--130Chapter3: Proteinsg l u t a m i ca c i delectrostaticattractionsRo//h y d r o g e nb o n dHHN-CH,tCH,van der Waalsattractionst-CHtt-tFigure3-4 Threetypes of noncovalentbonds help proteinsfold.
Althoughasingleone of thesebondsis quiteweak,many of them often form togethertocreatea strongbondingarrangement,asin the exampleshown.As in the previousfigure,R is usedasa generaldesignationfor an aminoacidsidechain.n':ProteinsFoldinto a Conformationof LowestEnergyAs a result of all of these interactions, most proteins have a particular threedimensional structure, which is determined by the order of the amino acids in itschain.
The final folded structure, or conformation, of any polypeptide chain isgenerally the one that minimizes its free energy. Biologists have studied proteinfolding in a test tube by using highly purified proteins. Treatment with certainsequence contains all the information needed for specifying the three-dimensional shape of a protein, which is a critical point for understanding cell function.Each protein normally folds up into a single stable conformation. However,the conformation changes slightly when the protein interacts with othermolecules in the cell. This change in shape is often crucial to the function of theprotein, as we see later.Although a protein chain can fold into its correct conformation without outside help, in a living cell special proteins called.molecular chaperonesoften assistin protein folding.
Molecular chaperones bind to partly folded polypeptidechains and help them progress along the most energetically ravoriute-rolaing-*<_hydrophobiccore regtoncontainsnonpotars i d ec h a i n sunfolded polypeptidep o l a rs i d ec h a i n son the outsideof the moleculecan form hydrogenbondsto waterfolded conformation in aqueousenvtronmentFigure3-5 How a protein folds into acompactconformation,The polaraminoacidsidechainstend to gatheron theoutsideof the protein,where they caninteractwith water;the nonpolaraminoacidsidechainsare buriedon the insideto form a tightly packedhydrophobiccore of atomsthat are hidden from water.In this schematicdrawing,the proteincontainsonly about30 aminoacids.131THESHAPEAND STRUCTUREOF PROTEINS(B)(A)oE X P O STEO A H I G HCONCENTRATIONO FU R E AC+HzNp u r i f i e dp r o t e i ni s o l a t e df r o mc el l sdenatu redproler no r i g i n a lc o n f o r m a t i o nof protein re-formspathway.
In the crowded conditions of the q,toplasm, chaperones prevent thetemporarily exposed hydrophobic regions in newly syrrthesizedprotein chainsfrom associatingwith each other to form protein aggregates(see p. 388). However, the final three-dimensional shape of the protein is still specified by itsamino acid sequence:chaperonessimplymake the folding processmore reliable.Proteins come in a wide variety of shapes,and they are generally between 50and 2000 amino acids long. Large proteins usually consist of severaldistinct protein domains-structural units that fold more or less independently of eachother, as we discussbelow Since the detailed structure of any protein is complicated, severaldifferent representationsare used to depict the proteins structure,each emphasizing different features.Panel 3-2 (pp.
132-133) presents four different representations of a proteindomain called SH2, which has important functions in eucaryotic cells. Constructed from a string of 100 amino acids, the structure is displayed as (A) apollpeptide backbone model, (B) a ribbon model, (C) a wire model thatincludes the amino acid side chains, and (D) a space-filling model. Each of thethree horizontal rows shows the protein in a different orientation, and theimage is colored in a way that allows the polypeptide chain to be followed fromits N-termints (purple) to its C-terminrs (red).<GTGA>Panel 3-2 shows that a protein's conformation is amazingly complex, evenfor a structure as small as the SH2 domain.
But the description of protein structures can be simplified because they are built up from combinations of severalcommon structural motifs, as we discuss next.Thea Helixand the B SheetAreCommonFoldingPatterns\Mhen we compare the three-dimensional structures of many different proteinmolecules, it becomes clear that, although the overall conformation of each protein is unique, two regular folding patterns are often found in parts of them.Both patterns were discovered more than 50 years ago from studies of hair andsilk. The first folding pattern to be discovered, called the c helix, was found inthe protein u-keratin, which is abundant in skin and its derivatives-such ashair, nails, and horns.
Within a year of the discovery of the cr helix, a secondfolded structure, called a p sheet, was found in the protein ftbroin, the majorconstituent of silk. These two patterns are particularly common because theyresult from hydrogen-bonding between the N-H and C=O groups in thepolypeptide backbone, without involving the side chains of the amino acids'Thus, many different amino acid sequences can form them. In each case, theprotein chain adopts a regular, repeating conformation. Figure 3-7 shows thesetwo conformations, as well as the abbreviations that are used to denote them inribbon models of proteins.The core of many proteins contains extensiveregions of p sheet.As shown inFigure 3-8, these B sheetscan form either from neighboring pollpeptide chainsthat run in the same orientation (parallel chains) or from a pollpeptide chainthat folds back and forth upon itself, with each section of the chain running inthe direction opposite to that of its immediate neighbors (antiparallel chains).Both types of B sheet produce a very rigid structure, held together by hydrogenbonds that connect the peptide bonds in neighboring chains (seeFigure 3-7D).r\n2Figure3-6 The refolding of adenatured protein.
(A)Thistype ofexperiment,first Performedmorethan 40 yearsago,demonstratesthat a Protein'sconformationisdeterminedsolelyby its aminoacid(B)The structureof urea.sequence.Ureais very solublein waterandunfoldsproteinsat highwherethereisconcentrations,aboutone ureamoleculefor everYsixwatermolecules.(A) Backbone:Showsthe overall organization of the polypeptidechain; a clean way to comparestructuresof related pioteins.(B) Ribbon:Easyway to visualizesecondarystructures,suchaso helicesand B sheets.c3-5oooEf(J( C ) W i r e : H i g h l i g h t ss i d ec h a i n sa n d t h e i r r e l a t i v ep r o x i m i t i e su; s e f u lf o rp r e d i c t i n gw h i c h a m i n o a c i d sm i g h t b e i n v o l v e di n a p r o t e i n ' sa c t i v i t y ,p a r t i c u l a r l yi f t h e p r o t e i ni s a n e n z y m e .(D) Space-filling:Providescontour map of the protein; givesa feel for thes h a o eo f t h e p r o t e i na n d s h o w sw h i c h a m i n o a c i ds i d ec h a i n sa r e e x p o s e don its surface.Showshow the protein might look to a small molecule,suchas water, or to another protein.134Chapter3: Proteinsa m i n oa c i ds i d ec h a i n(c)IillliFigure3-7 The regular conformation of the polypeptide backbone in the cr helix and the p sheet.<GTAG><TGCT>(A,B,and C)The o helix.The N-H of every peptide bond is hydrogen-bondedto the C=Oof i neighboringpeptidebondlocatedfour peptidebondsawayin the samechain.Notethat all of the N-H groupspoint up in this diagIm and that all ofthe C=Ogroupspoint down (towardthe C-terminus);this givesa polarityto the helix,with the C-terminushavinga partialnegativeand the N-terminusa partialpositivecharge.(D,E,and F)TheF sheet.In this example,adjacentpeptidechainsrun in opposite(antiparallel)directions.Hydrogen-bondingbetweenpeptidebondsin differentstrandsholdstneindividualpolypeptidechains(strands)togetherin a B sheet,and the aminoacidsidechainsin eachstrandalternatetyprojectaboveand belowthe planeofthe sheet.(A)and (D)showall the atomsin the polypeptidebackbone,but theaminoacidsidechainsaretruncatedand denotedby R.In contrast,(B)and (E)showthe backboneatomsonly,while (C)and (F)displaythe shorthandsymbolsthat areusedto representthe s helixand the B sheetin ribbondrawingsof proteins(seePanel3-28).'.':,'',.:'r,r,ANDSTRUCTURE''OFI'PROTEINS,,],.':,THESHAPE,135An a helix is generatedwhen a single polypeptide chain twists around onitself to form a rigid cylinder.A hydrogenbond forms betweeneveryfourth peptide bond, linking the C=Oof one peptidebond to the N-H of another(seeFigure 3-7A).This givesrise to a regularhelix with a completeturn every3.6 aminoacids.
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