Introduction to Protein Structure

Автор(ы):Branden C., Tooze J.
06.10.2007
Год изд.:1999
Издание:2
Описание: The fundamental tenet of molecular biology, namely that one cannot really understand biological reactions without understanding the structure of the participating molecules, is at last being vindicated. As the database of known protein structures rapidly expands, so does the range of biological pathways about which we can ask meaningful questions at close to atomic levels of resolution. An understanding of the principles of protein structure is becoming of ever widening significance to molecular biology. The growth in the interest in high-resolution protein structure over the past decade and the reception of the first edition have encouraged to prepare a new edition of this book. Universities are devoting more time to courses specifically on protein structure, or increasing the amount of time given to protein structure in more generally based biology and biochemistry courses. The authors hope that this new edition of Introduction to Protein Structure will prove useful both to teachers and students.
Оглавление:
Introduction to Protein Structure — обложка книги.
Part I Basic Structural Principles [1]
  1. The Building Blocks [3]
    Proteins are polypeptide chains [4]
    The genetic code specifies 20 different amino acid side chains [4]
    Cysteines can form disulfide bridges [5]
    Peptide units are building blocks of protein structures [8]
    Glycine residues can adopt many different conformations [9]
    Certain side-chain conformations are energetically favorable [10]
    Many proteins contain intrinsic metal atoms [11]
    Conclusion [12]
    Selected readings [12]
  2. Motifs of Protein Structure [13]
    The interior of proteins is hydrophobic [14]
    The alpha ((?)) helix is an important element of secondary structure [14]
    The (?) helix has a dipole moment [16]
    Some amino acids are preferred in (?) helices [16]
    Beta ((?)) sheets usually have their (?) strands either parallel or antiparallel [19]
    Loop regions are at the surface of protein molecules [21]
    Schematic pictures of proteins highlight secondary structure [22]
    Topology diagrams are useful for classification of protein structures [23]
    Secondary structure elements are connected to form simple motifs [24]
    The hairpin p motif occurs frequently in protein structures [26]
    The Greek key motif is found in antiparallel (?) sheets [27]
    The (?)-(?)-(?) motif contains two parallel (?) strands [27]
    Protein molecules are organized in a structural hierarchy [28]
    Large polypeptide chains fold into several domains [29]
    Domains are built from structural motifs [30]
    Simple motifs combine to form complex motifs [30]
    Protein structures can be divided into three main classes [31]
    Conclusion [32]
    Selected readings [33]
  3. Alpha-Domain Structures [35]
    Coiled-coil (?) helices contain a repetitive heptad amino acid sequence pattern [35]
    The four-helix bundle is a common domain structure in ex proteins [37]
    Alpha-helical domains are sometimes large and complex [39]
    The globin fold is present in myoglobin and hemoglobin [40]
    Geometric considerations determine ex-helix packing [40]
    Ridges of one a helix fit into grooves of an adjacent helix [40]
    The globin fold has been preserved during evolution [41]
    The hydrophobic interior is preserved [42]
    Helix movements accommodate interior side-chain mutations [43]
    Sickle-cell hemoglobin confers resistance to malaria [43]
    Conclusion [45]
    Selected readings [45]
  4. Alpha/Beta Structures [47]
    Parallel p strands are arranged in barrels or sheets [47]
    Alpha/beta barrels occur in many different enzymes [48]
    Branched hydrophobic side chains dominate the core of (?)/(?) barrels [49]
    Pyruvate kinase contains several domains, one of which is an (?)/(?) barrel [51]
    Double barrels have occurred by gene fusion [52]
    The active site is formed by loops at one end of the (?)/(?) barrel [53]
    Alpha/beta barrels provide examples of evolution of new enzyme activities [54]
    Leucine-rich motifs form an (?)/(?)-horseshoe fold [55]
    Alpha/beta twisted open-sheet structures contain a helices on both sides of the (?) sheet [56]
    Open (?)-sheet structures have a variety of topologies [57]
    The positions of active sites can be predicted in (?)/(?) structures [57]
    Tyrosyl-tRNA synthetase has two different domains ((?)/(?)+a) [59]
    Carboxypeptidase is an (?)/(?) protein with a mixed P sheet [60]
    Arabinose-binding protein has two similar (?)/(?) domains [62]
    Conclusion [63]
    Selected readings [64]
  5. Beta Structures [67]
    Up-and-down barrels have a simple topology [68]
    The retinol-binding protein binds retinol inside an up-and-down (?) barrel [68]
    Amino acid sequence reflects p structure [69]
    The retinol-binding protein belongs to a superfamily of protein structures [70]
    Neuraminidase folds into up-and-down p sheets [70]
    Folding motifs form a propeller-like structure in neuraminidase [71]
    The active site is in the middle of one side of the propeller [72]
    Greek key motifs occur frequently in antiparallel (?) structures [72]
    The (?)-crystallin molecule has two domains [74]
    The domain structure has a simple topology [74]
    Two Greek key motifs form the domain [74]
    The two domains have identical topology [75]
    The two domains have similar structures [76]
    The Greek key motifs in (?) crystallin are evolutionarily related [76]
    The Greek key motifs can form jelly roll barrels [77]
    The jelly roll motif is wrapped around a barrel [77]
    The jelly roll barrel is usually divided into two sheets [78]
    The functional hemagglutinin subunit has two polypeptide chains [79]
    The subunit structure is divided into a stem and a tip [79]
    The receptor binding site is formed by the jelly roll domain [80]
    Hemagglutinin acts as a membrane fusogen [80]
    The structure of hemagglutinin is affected by pH changes [81]
    Parallel (?)-helix domains have a novel fold [84]
    Conclusion [85]
    Selected readings [87]
  6. Folding and Flexibility [89]
    Globular proteins are only marginally stable [90]
    Kinetic factors are important for folding [91]
    Molten globules are intermediates in folding [92]
    Burying hydrophobic side chains is a key event [93]
    Both single and multiple folding pathways have been observed [93]
    Enzymes assist formation of proper disulfide bonds during folding [96]
    Isomerization of proline residues can be a rate-limiting step in protein folding [98]
    Proteins can fold or unfold inside chaperonins [99]
    GroEL is a cylindrical structure with a central channel in which newly synthesized polypeptides bind [100]
    GroES closes off one end of the GroEL cylinder [102]
    The GroEL-GroES complex binds and releases newly synthesized polypeptides in an ATP-dependent cycle [102]
    The folded state has a flexible structure [104]
    Conformational changes in a protein kinase are important for cell cycle regulation [105]
    Peptide binding to calmodulin induces a large interdomain movement [109]
    Serpins inhibit serine proteinases with a spring-loaded safety catch mechanism [110]
    Effector molecules switch allosteric proteins between R and Т states [113]
    X-ray structures explain the allosteric properties of phosphofructokinase [114]
    Conclusion [117]
    Selected readings [119]
  7. DNA Structures [121]
    The DNA double helix is different in A- and B-DNA [121]
    The DNA helix has major and minor grooves [122]
    Z-DNA forms a zigzag pattern [123]
    B-DNA is the preferred conformation in vivo [124]
    Specific base sequences can be recognized in B-DNA [124]
    Conclusion [125]
    Selected readings [126]
Part 2 Structure, Function, and Engineering [127]
  8. DNA Recognition in Procaryotes by Helix-Turn-Helix Motifs [129]
    A molecular mechanism for gene control [129]
    Repressor and Cro proteins operate a procaryotic genetic switch region [130]
    The x-ray structure of the complete lambda Cro protein is known [131]
    The x-ray structure of the DNA-binding domain of the lambda repressor is known [132]
    Both lambda Cro and repressor proteins have a specific DNA-binding motif [133]
    Model building predicts Cro-DNA interactions [134]
    Genetic studies agree with the structural model [135]
    The x-ray structure of DNA complexes with 434 Cro and repressor revealed novel features of protein-DNA interactions [136]
    The structures of 434 Cro and the 434 repressor DNA-binding domain are very similar [137]
    The proteins impose precise distortions on the B-DNA in the complexes [138]
    Sequence-specific protein-DNA interactions recognize operator regions [138]
    Protein-DNA backbone interactions determine DNA conformation [139]
    Conformational changes of DNA are important for differential binding of repressor and Cro to different operator sites [140]
    The essence of phage repressor and Cro [141]
    DNA binding is regulated by allosteric control [142]
    The trp repressor forms a helix-turn-helix motif [142]
    A conformational change operates a functional switch [142]
    Lac repressor binds to both the major and minor grooves inducing a sharp bend in the DNA [143]
    CAP-induced DNA bending could activate transcription [146]
    Conclusion [147]
    Selected readings [148]
  9. DNA Recognition by Eucaryotic Transcription Factors [151]
    Transcription is activated by protein-protein interactions [152]
    The TATA box-binding protein is ubiquitous [153]
    The three-dimensional structures of TBP-TATA box complexes are known [154]
    A (?) sheet in TBP forms the DNA-binding site [154]
    TBP binds in the minor groove and induces large structural changes in DNA [155]
    The interaction area between TBP and the TATA box is mainly hydrophobic [157]
    Functional implications of the distortion of DNA by TBP [158]
    TFIIA and TFIIB bind to both TBP and DNA [159]
    Homeodomain proteins are involved in the development of many eucaryotic organisms [159]
    Monomers of homeodomain proteins bind to DNA through a helix-turn-helix motif [160]
    In vivo specificity of homeodomain transcription factors depends on interactions with other proteins [162]
    POU regions bind to DNA by two tandemly oriented helix-turn-helix motifs [164]
    Much remains to be learnt about the function of homeodomains in vivo [166]
    Understanding tumorigenic mutations [166]
    The monomeric p53 polypeptide chain is divided in three domains [167]
    The oligomerization domain forms tetramers [167]
    The DNA-binding domain of p53 is an antiparallel P barrel [168]
    Two loop regions and one a helix of p53 bind to DNA [169]
    Tumorigenic mutations occur mainly in three regions involved in DNA binding [170]
    Conclusions [172]
    Selected readings [172]
  10. Specific Transcription Factors Belong to a Few Families [175]
    Several different groups of zinc-containing motifs have been observed [176]
    The classic zinc fingers bind to DNA in tandem along the major groove [177]
    The finger region of the classic zinc finger motif interacts with DNA [178]
    Two zinc-containing motifs in the glucocorticoid receptor form one DNA-binding domain [181]
    A dimer of the glucocorticoid receptor binds to DNA [183]
    An a helix in the first zinc motif provides the specific protein-DNA interactions [184]
    Three residues in the recognition helix provide the sequence-specific interactions with DNA [184]
    The retinoid X receptor forms heterodimers that recognize tandem repeats with variable spacings [185]
    Yeast transcription factor GAL4 contains a binuclear zinc cluster in its DNA-binding domain [187]
    The zinc cluster regions of GAL4 bind at the two ends of the enhancer element [188]
    The linker region also contributes to DNA binding [189]
    DNA-binding site specificity among the С(?)-zinc cluster family of transcription factors is achieved by the linker regions [190]
    Families of zinc-containing transcription factors bind to DNA in several different ways [191]
    Leucine zippers provide dimerization interactions for some eucaryotic transcription factors [191]
    The GCN4 basic region leucine zipper binds DNA as a dimer of two uninterrupted a helices [193]
    GCN4 binds to DNA with both specific and nonspecific contacts [194]
    The HLH motif is involved in homodimer and heterodimer associations [196]
    The (?)-helical basic region of the (?)/HLH motif binds in the major groove of DNA [198]
    The (?)/HLH/zip family of transcription factors have both HLH and leucine zipper dimerization motifs [199]
    Max and MyoD recognize the DNA HLH consensus sequence by different specific protein-DNA interactions [201]
    Conclusion [201]
    Selected readings [203]
  11. An Example of Enzyme Catalysis: Serine Proteinases [205]
    Proteinases form four functional families [205]
    The catalytic properties of enzymes are reflected in K(?) and k(?) values [206]
    Enzymes decrease the activation energy of chemical reactions [206]
    Serine proteinases cleave peptide bonds by forming tetrahedral transition states [208]
    Four important structural features are required for the catalytic action of serine proteinases [209]
    Convergent evolution has produced two different serine proteinases with similar catalytic mechanisms [210]
    The chymotrypsin structure has two antiparallel (?)-barrel domains [210]
    The active site is formed by two loop regions from each domain [211]
    Did the chymotrypsin molecule evolve by gene duplication? [212]
    Different side chains in the substrate specificity pocket confer preferential cleavage [212]
    Engineered mutations in the substrate specificity pocket change the rate of catalysis [213]
    The Asp 189-Lys mutation in trypsin causes unexpected changes in substrate specificity [215]
    The structure of the serine proteinase subtilisin is of the(?)/(?) type [215]
    The active sites of subtilisin and chymotrypsin are similar [216]
    A structural anomaly in subtilisin has functional consequences [217]
    Transition-state stabilization in subtilisin is dissected by protein engineering [217]
    Catalysis occurs without a catalytic triad [217]
    Substrate molecules provide catalytic groups in substrate-assisted catalysis [218]
    Conclusion [219]
    Selected readings [220]
  12. Membrane Proteins [223]
    Membrane proteins are difficult to crystallize [224]
    Novel crystallization methods are being developed [224]
    Two-dimensional crystals of membrane proteins can be studied by electron microscopy [225]
    Bacteriorhodopsin contains seven transmembrane (?) helices [226]
    Bacteriorhodopsin is a light-driven proton pump [227]
    Porins form transmembrane channels by (?) strands [228]
    Porin channels are made by up and down (?) barrels [229]
    Each porin molecule has three channels [230]
    Ion channels combine ion selectivity with high levels of ion conductance [232]
    The K(?) channel is a tetrameric molecule with one ion pore in the interface between the four subunits [232]
    The ion pore has a narrow ion selectivity filter [233]
    The bacterial photosynthetic reaction center is built up from four different polypeptide chains and many pigments [234]
    The L, M, and H subunits have transmembrane (?) helices [236]
    The photosynthetic pigments are bound to the L and M subunits [237]
    Reaction centers convert light energy into electrical energy by electron flow through the membrane [239]
    Antenna pigment proteins assemble into multimeric light-harvesting particles [240]
    Chlorophyll molecules form circular rings in the light-harvesting complex LH2 [241]
    The reaction center is surrounded by a ring of 16 antenna proteins of the light-harvesting complex LH1 [242]
    Transmembrane a helices can be predicted from amino acid sequences [244]
    Hydrophobicity scales measure the degree of hydrophobicity of different amino acid side chains [245]
    Hydropathy plots identify transmembrane helices [245]
    Reaction center hydropathy plots agree with crystal structural data [246]
    Membrane lipids have no specific interaction with protein transmembrane a helices [246]
    Conclusion [247]
    Selected readings [248]
  13. Signal Transduction [251]
    G proteins are molecular amplifiers [252]
    Ras proteins and the catalytic domain of G(?) have similar three-dimensional [254]
    structures G(?) is activated by conformational changes of three switch regions [257]
    GTPases hydrolyze GTP through nucleophilic attack by a water molecule [259]
    The Gp subunit has a seven-blade propeller fold, built up from seven WD repeat units [261]
    The GTPase domain of G(?) binds to Gp in the heterotrimeric G(?) complex [263]
    Phosducin regulates light adaptation in retinal rods [265]
    Phosducin binding to G(?) blocks binding of G(?) [265]
    The human growth hormone induces dimerization of its cognate receptor [267]
    Dimerization of the growth hormone receptor is a sequential process [268]
    The growth hormone also binds to the prolactin receptor [269]
    Tyrosine kinase receptors are important enzyme-linked receptors [270]
    Small protein modules form adaptors for a signaling network [272]
    SH2 domains bind to phosphotyrosinecontaining regions of target molecules [273]
    SH3 domains bind to proline-rich regions of target molecules [274]
    Src tyrosine kinases comprise SH2 and SH3 domains in addition to a tyrosine kinase [275]
    The two domains of the kinase in the inactive state are held in a closed conformation by assembly of the regulatory domains [277]
    Conclusion [278]
    Selected readings [280]
  14. Fibrous Proteins [283]
    Collagen is a superhelix formed by three parallel, very extended left-handed helices [284]
    Coiled coils are frequently used to form oligomers of fibrous and globular proteins [286]
    Amyloid fibrils are suggested to be built up from continuous P sheet helices [288]
    Spider silk is nature's high-performance fiber [289]
    Muscle fibers contain myosin and actin which slide against each other during muscle contraction [290]
    Myosin heads form cross-bridges between the actin and myosin filaments [291]
    Time-resolved x-ray diffraction of frog muscle confirmed movement of the cross-bridges [292]
    Structures of actin and myosin have been determined [293]
    The structure of myosin supports the swinging cross-bridge hypothesis [295]
    The role of ATP in muscular contraction has parallels to the role of GTP in G-protein activation [296]
    Conclusion [297]
    Selected readings [298]
  15. Recognition of Foreign Molecules by the Immune System [299]
    The polypeptide chains of antibodies are divided into domains [300]
    Antibody diversity is generated by several different mechanisms [302]
    All immunoglobulin domains have similar three-dimensional structures [303]
    The immunoglobulin fold is best described as two antiparallel (?) sheets packed tightly against each other [304]
    The hypervariable regions are clustered in loop regions at one end of the variable domain [305]
    The antigen-binding site is formed by close association of the hypervariable regions from both heavy and light chains [306]
    The antigen-binding site binds haptens in crevices and protein antigens on large flat surfaces [308]
    The CDR loops assume only a limited range of conformations, except for the heavy chain CDR3 [311]
    An IgG molecule has several degrees of conformational flexibility [312]
    Structures of MHC molecules have provided insights into the molecular mechanisms of (?)-cell activation [312]
    MHC molecules are composed of antigen-binding and immunoglobulin-like domains [313]
    Recognition of antigen is different in MHC molecules compared with immunoglobulins [314]
    Peptides are bound differently by class I and class II MHC molecules [315]
    T-cell receptors have variable and constant immunoglobulin domains and hypervariable regions [316]
    MHC-peptide complexes are the ligands for T-cell receptors [318]
    Many cell-surface receptors contain immunoglobulin-like domains [318]
    Conclusion [320]
    Selected readings [321]
  16. The Structure of Spherical Viruses [325]
    The protein shells of spherical viruses have icosahedral symmetry [327]
    The icosahedron has high symmetry [327]
    The simplest virus has a shell of 60 protein subunits [328]
    Complex spherical viruses have more than one polypeptide chain in the asymmetric unit [329]
    Structural versatility gives quasi-equivalent packing in Т=3 plant viruses [331]
    The protein subunits recognize specific parts of the RNA inside the shell [332]
    The protein capsid of picornaviruses contains four polypeptide chains [333]
    There are four different structural proteins in picornaviruses [334]
    The arrangement of subunits in the shell of picornaviruses is similar to that of Т = 3 plant viruses [334]
    The coat proteins of many different spherical plant and animal viruses have similar jelly roll barrel structures, indicating an evolutionary relationship [335]
    Drugs against the common cold may be designed from the structure of rhinovirus [337]
    Bacteriophage MS2 has a different subunit structure [339]
    A dimer of MS2 subunits recognizes an RNA packaging signal [339]
    The core protein of alphavirus has a chymotrypsin-like fold [340]
    SV40 and polyomavirus shells are constructed from pentamers of the major coat protein with nonequivalent packing but largely equivalent interactions [341]
    Conclusion [343]
    Selected readings [344]
  17. Prediction, Engineering, and Design of Protein Structures [347]
    Homologous proteins have similar structure and function [348]
    Homologous proteins have conserved structural cores and variable loop regions [349]
    Knowledge of secondary structure is necessary for prediction of tertiary structure [350]
    Prediction methods for secondary structure benefit from multiple alignment of homologous proteins [351]
    Many different amino acid sequences give similar three-dimensional structures [352]
    Prediction of protein structure from sequence is an unsolved problem [352]
    Threading methods can assign amino acid sequences to known three-dimensional folds [353]
    Proteins can be made more stable by engineering [354]
    Disulfide bridges increase protein stability [355]
    Glycine and proline have opposite effects on stability [356]
    Stabilizing the dipoles of a helices increases stability [357]
    Mutants that fill cavities in hydrophobic cores do not stabilize (?) lysozyme [358]
    Proteins can be engineered by combinatorial methods [358]
    Phage display links the protein library to DNA [359]
    Affinity and specificity of proteinase inhibitors can be optimized by phage display [361]
    Structural scaffolds can be reduced in sizewhile function is retained [363]
    Phage display of random peptide libraries identified agonists of erythropoetin receptor [364]
    DNA shuffling allows accelerated evolution of genes [365]
    Protein structures can be designed from first principles [367]
    A (?) structure has been converted to an a structure by changing only half of the sequence [368]
    Conclusion [370]
    Selected readings [371]
  18. Determination of Protein Structures [373]
    Several different techniques are used to study the structure of protein molecules [373]
    Protein crystals are difficult to grow [374]
    X-ray sources are either monochromatic or polychromatic [376]
    X-ray data are recorded either on image plates or by electronic detectors [377]
    The rules for diffraction are given by Bragg's law [378]
    Phase determination is the major crystallographic problem [379]
    Phase information can also be obtained by Multiwavelength Anomalous Diffraction experiments [381]
    Building a model involves subjective interpretation of the data [381]
    Errors in the initial model are removed by refinement [383]
    Recent technological advances have greatly influenced protein crystallography [383]
    X-ray diffraction can be used to study the structure of fibers as well as crystals [384]
    The structure of biopolymers can be studied using fiber diffraction [386]
    NMR methods use the magnetic properties of atomic nuclei [387]
    Two-dimensional NMR spectra of proteins are interpreted by the method of sequential assignment [389]
    Distance constraints are used to derive possible structures of a protein molecule [390]
    Biochemical studies and molecular structure give complementary functional information [391]
    Conclusion [391]
    Selected readings [392]
Protein Structure on the World Wide Web [393]
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