2 Структура и функция белка (1160071), страница 14
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A number of similar substructures(domains) occur in many functionally unrelated proteins. An exampleis a 40 to 45 amino acid sequence called the EGF (epidermal growthfactor) domain that makes up part of the structure of urokinase, thelow-density lipoprotein receptor, several proteins involved in bloodclotting, and many others. These domains often fold up into structuralconfigurations that have an unusual degree of stability or that arespecialized for a certain environment. Evolutionary relationships canalso be inferred from the structural and functional similarities withinprotein families.Certain amino acid sequences often serve as signals that determine the cellular location, chemical modification, and half-life of a protein.
Special signal sequences, usually at the amino terminus, are usedto target certain proteins for export from the cell, while other proteinsare distributed to the nucleus, the cell surface, the cytosol, and othercellular locations. Other sequences act as attachment sites for prosthetic groups, such as glycosyl groups in glycoproteins and lipids inlipoproteins. Some of these signals are well characterized, and are easily recognized if they occur in the sequence of a newly discovered protein.The probability that information about a new protein can bededuced from its primary structure improves constantly with the almost daily addition to the number of published amino acid sequencesstored in shared databanks.154Part II Structure and CatalysisHomologous Proteins from Different SpeciesHave Homologous SequencesFigure 6-15 The amino acid sequence of humancytochrome c. Amino acid substitutions found atdifferent positions in the cytochrome c of other species are listed below the sequence of the humanprotein.
The amino acids are color-coded to helpdistinguish conservative and nonconservative substitutions: invariant amino acids are shaded in yellow, conservative amino acid substitutions areshaded in blue, and nonconservative substitutionsare unshaded. X is an unusual amino acid, trimethyllysine. The one-letter abbreviations for aminoacids are used here (see Table 5-1).151015GDVE KGKK I F I MKN I DA ATV VQ RT TSAAN ENLP K STKST T5055AAN KN K G IDI S R AVEQMNKANTRAI WLVTNQE20c As QL CE E6065GANQDEKE D T L• MD E NM [ SNNFYQPKRSeveral important conclusions have come from study of the amino acidsequences of homologous proteins from different species. Homologousproteins are those that are evolutionarily related. They usually perform the same function in different species; an example is hemoglobin,which has the same oxygen-transport function in different vertebrates.Homologous proteins from different species often have polypeptidechains that are identical or nearly identical in length.
Many positionsin the amino acid sequence are occupied by the same amino acid in allspecies and are thus called invariant residues. But in other positionsthere may be considerable variation in the amino acid from one speciesto another; these are called variable residues.The functional significance of sequence homology can be illustrated by cytochrome c, an iron-containing mitochondrial proteinthat transfers electrons during biological oxidations in eukaryoticcells. The polypeptide chain of this protein has a molecular weight ofabout 13,000 and has about 100 amino acid residues in most species.The amino acid sequences of cytochrome c from over 60 different species have been determined, and 27 positions in the chain of amino acidresidues are invariant in all species tested (Fig.
6-15), suggesting thatthey are the most important residues specifying the biological activityof cytochrome c. The residues in other positions in the chain exhibitsome interspecies variation. There are clear gradations in the numberof changes observed in the variable residues. In some positions, allsubstitutions involve similar amino acid residues (e.g., Arg will replaceLys, both of which are positively charged); these are called conservative substitutions. At other positions the substitutions are more random.
As we will show in the next chapter, the polypeptide chains ofproteins are folded into characteristic and specific conformations andthese conformations depend on amino acid sequence. Clearly, the invariant residues are more critical to the structure and function of aprotein than the variable ones. Recognizing which amino acids fall intoeach category is an important step in deciphering the complicatedquestion of how amino acid sequence is translated into a specific threedimensional structure.The variable amino acids provide information of another sort. Evolution is sometimes regarded as a theory that is accepted but difficultto test, yet the phylogenetic trees established by taxonomy have beentested and experimentally confirmed through biochemistry.
The exam-25H T V E K GGG I DN N LCGA AE G7030354045K H K T G P N L H G L F G R K T G Q A P G Y S YTGQ QA NI Y IH Ss vv F AT SPISF IQTTATVEwYD75808590Q95100E Y L E N P K K Y I P G T K M: i F V G I K K K E E R A D L I A Y LKK A T NTV AL ST D D G N I V T F ML D K S SDILA GX A TVE TcKPP NTAQ S AATE SSEQDQNTAEGKEKASChapter 6 An Introduction to Proteinsination of sequences of cytochrome c and other homologous proteinshas led to an important conclusion: the number of residues that differin homologous proteins from any two species is in proportion to thephylogenetic difference between those species.
For example, 48 aminoacid residues differ in the cytochrome c molecules of the horse and ofyeast, which are very widely separated species, whereas only two residues differ in the cytochrome c of the much more closely related duckand chicken. In fact, the cytochrome c molecule has identical aminoacid sequences in the chicken and the turkey, and in the pig, cow, andsheep. Information on the number of residue differences between homologous proteins of different species allows the construction of evolutionary maps that show the origin and sequence of development ofdifferent animals and plants during the evolution of species (Fig.
6 16). The relationships established by taxonomy and biochemistry agreewell.MammalsFigure 6—16 Main branches of the evolutionarytree constructed from the number of amino acid differences between cytochrome c molecules of different species. The numbers represent the number ofresidues by which the cytochrome c of a given lineof organism differs from its ancestors.,_ ,MonkeyHomo sapiens,chimp2Mouse1554Birds andOstrichreptiles5 KangarooChicken, turkeyEmu1RabbitPenguinPigeon3~ Turtle2 -,6Duck - ' 1Rattlesnake1Horse, pig, sheep, cowDog, seal, batloHippopotamus6Bony C„a rfishesPTuna1DogfishCartilaginousfishesAmphibiansBullfrogLampreyStarfishMoth,hawkmothEarthworm23Honey beeInsectsFly16Locust16YeastFungi15Candida - -714NeurosporaWheat13••Sesame SunflowerRice3127Plants1.
^Humicola1231113310SpinachGinkgo156Part II Structure and CatalysisSummaryCells generally contain thousands of different proteins, each with a different function or biologicalactivity. These functions include enzymatic catalysis, molecular transport, nutrition, cell or organismal motility, structural roles, organismal defense,regulation, and many others. Proteins consist ofvery long polypeptide chains having from 100 toover 2,000 amino acid residues joined by peptidelinkages. Some proteins have several polypeptidechains, which are then referred to as subunits.Simple proteins yield only amino acids on hydrolysis; conjugated proteins contain in addition someother component, such as a metal ion or organicprosthetic group.Proteins are purified by taking advantage ofproperties in which they differ, such as size, shape,binding affinities, charge, etc.
Purification alsorequires a method for quantifying or assaying aparticular protein in the presence of others. Proteins can be both separated and visualized by electrophoretic methods. Antibodies that specificallybind a certain protein can be used to detect andlocate that protein in a solution, a gel, or even inthe interior of a cell.All proteins are made from the same set of 20amino acids.
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