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Showing papers by "Laboratory of Molecular Biology published in 1969"


Journal ArticleDOI
20 Jun 1969-Science
TL;DR: There is now a real possibility of solving the problem in complete detail, provided a way can be found to crystallize a recently purified globular subfragment of the myosin molecule, and some apparently paradoxical properties of the system are revealed.
Abstract: During the last few years the basic features of the sliding-filament model of contraction in striated muscle have gained general acceptance and it has been possible to concentrate attention on the detailed mechanism by which the relative sliding force between the actin and myosin filaments is developed. A number of observations have indicated in general outline how crossbridges between the filaments may be involved in the generation of this force but have also revealed some apparently paradoxical properties of the system. The most recent findings show a possible way in which these paradoxes can be resolved. Furthermore, there is now a real possibility of solving the problem in complete detail, provided a way can be found to crystallize a recently purified globular subfragment of the myosin molecule. In this article I discuss these new findings and their implications. According to the interdigitating filament model of striated muscle (1), the contractile material consists of long series of partially overlapping arrays of actin and myosin filaments which form the myofibrils. These overlapping arrays give rise to the characteristic band pattern visible in the light microscope. In vertebrate striated muscle the myosin-containing filaments are spaced out in a hexagonal lattice 400 The Mechanism of Muscular Contraction

1,615 citations


Journal ArticleDOI
25 Jan 1969-Nature
TL;DR: Polarization of the system due to the buried negative charge of the aspartic acid residue would make the serine oxygen strongly nucleophilic and would explain its reactivity towards amides and esters.
Abstract: The catalytic site of chymotrypsin contains an interior aspartic acid hydrogen-bonded to a histidine which in its turn is hydrogen-bonded to a serine. Polarization of the system due to the buried negative charge of the aspartic acid residue would make the serine oxygen strongly nucleophilic and would explain its reactivity towards amides and esters.

967 citations


Journal ArticleDOI
01 Mar 1969-Nature
TL;DR: Autoradiography has revealed in a stringent strain of E. coli two compounds that seem to be involved in the inhibition of the synthesis of RNA.
Abstract: Autoradiography has revealed in a stringent strain of E. coli two compounds that seem to be involved in the inhibition of the synthesis of RNA.

690 citations


Journal ArticleDOI
06 Dec 1969-Nature
TL;DR: The initiator regions of the three cistrons of R17 bacteriophage RNA have been isolated and sequenced and contain a UGA triplet as well as the expected AUG and two contain the sequence GGUUUGA.
Abstract: The initiator regions of the three cistrons of R17 bacteriophage RNA have been isolated and sequenced. All three regions contain a UGA triplet as well as the expected AUG and two contain the sequence GGUUUGA. The initiator regions thus represent untranslated sequences between termination and initiation codons.

595 citations


Journal ArticleDOI
TL;DR: Comparison of properties of the system regulating the synthesis of these compounds with those of the amino acid control of RNA biosynthesis suggests that the unusual compounds participate in an early step in the mechanism which leads to the slowing ofRNA biosynthesis during amino acid starvation of stringent strains.

443 citations


Journal ArticleDOI
TL;DR: A two-dimensional fractionation procedure has been developed for separating radioactively-labelled oligonucleotides of up to 50 residues long, using uniformly 32P-labelling 5S RNA of Escherichia coli as a model compound.
Abstract: A two-dimensional fractionation procedure has been developed for separating radioactively-labelled oligonucleotides of up to 50 residues long, using uniformly 32P-labelled 5S RNA of Escherichia coli as a model compound. The method uses ionophoresis on cellulose acetate at pH 3.5 in the first dimension; and ascending chromatography with a concentrated mixture of oligonucleotides on thin layers of mixed DEAE-cellulose and cellulose in the second dimension.

412 citations


Journal ArticleDOI
22 Nov 1969-Nature
TL;DR: A new model for transfer ribonucleic acid seems to explain the available experimental evidence better than do the models proposed hitherto.
Abstract: A new model for transfer ribonucleic acid seems to explain the available experimental evidence better than do the models proposed hitherto.

382 citations


Journal ArticleDOI
TL;DR: The unblocking reaction can be used as the basis for a ;diagonal'-electrophoretic separation of lysine peptides and N-terminal peptides, as shown by studies with beta-melanocyte-stimulating hormone.
Abstract: 1. Maleic anhydride was shown to react rapidly and specifically with amino groups of proteins and peptides. Complete substitution of chymotrypsinogen was achieved under mild conditions and the extent of reaction could be readily determined from the spectrum of the maleyl-protein. 2. Maleyl-proteins are generally soluble and disaggregated at neutral pH. Trypsin splits the blocked proteins only at arginine residues and there is frequently selectivity in this cleavage, e.g. in yeast alcohol dehydrogenase and pig glyceraldehyde 3-phosphate dehydrogenase. 3. The group is removed by intramolecular catalysis at acid pH. The half-time was 11-12hr. at 37 degrees at pH3.5 in in-maleyl-lysine or in maleyl-chymotrypsinogen. 4. The unblocking reaction can be used as the basis for a ;diagonal'-electrophoretic separation of lysine peptides and N-terminal peptides, as shown by studies with beta-melanocyte-stimulating hormone.

378 citations


Journal ArticleDOI
TL;DR: It is concluded that the modification of the base adjacent to the anticodon in tyrosine transfer RNA is essential for its efficient binding to ribosomes, but not for itsefficient charging.

352 citations


Journal ArticleDOI
TL;DR: Charge considerations, enzyme degradation studies, and labilities in acid and alkali lead to a structural assignment for MS I of guanosine 5'-diphosphate or 3'- or 2'-dphosphate (ppGpp).

352 citations


Journal ArticleDOI
TL;DR: A detailed analysis of the binding of N-formyl-l-tryptophan to the active site of α-chymotrypsin shows that the indolyl side chain lies in a hydrophobic pocket or slit, which accounts for the specificity of this enzyme for binding arginine or lysine side chains.

Journal ArticleDOI
TL;DR: Developing poly(ethylene)imine cellulose thin layers with phosphate solutions gives improved resolution of complex mixtures of nucleotides and minimizes the tailing of highly radioactive orthophosphate present in the mixtures and thus facilitates chromatographic analysis of crude acid extracts of phosphate-labeled bacteria.

Journal ArticleDOI
06 Sep 1969-Nature
TL;DR: The sequence of fifty-seven nucleotides in the coat protein cistron of phage R17 RNA directly confirms the genetic code, shows that the code used by the phage is degenerate and suggests that highly ordered base-paired structures exist in this RNA.
Abstract: The sequence of fifty-seven nucleotides in the coat protein cistron of phage R17 RNA directly confirms the genetic code, shows that the code used by the phage is degenerate and suggests that highly ordered base-paired structures exist in this RNA. Such base-paired loops may be involved in regulation of cistron expression and packing of the RNA in the phage particle.

Journal ArticleDOI
28 Jun 1969-Nature
TL;DR: Blocking of the α-amino groups by cyanate inhibits the uptake of CO2 by haemoglobin and inhibits the influence which changes in pCO2 at constant pH normally have on the oxygen affinity and on the Bohr effect.
Abstract: Blocking of the α-amino groups by cyanate inhibits the uptake of CO2 by haemoglobin. It also inhibits the influence which changes in pCO2 at constant pH normally have on the oxygen affinity and on the Bohr effect. Blocking the α-amino groups of the α chain reduces the alkaline Bohr effect by 25 per cent.

Journal ArticleDOI
28 Jun 1969-Nature
TL;DR: The imidazole groups of the C-terminal histidines of the β-chains, together with the α-amino groups ofThe α- chains, are responsible for most of the Bohr effect.
Abstract: The imidazole groups of the C-terminal histidines of the β-chains, together with the α-amino groups of the α-chains, are responsible for most of the Bohr effect. In oxyhaemoglobin these groups are free, while in deoxyhaemoglobin their pKs are raised, probably by linkage to carboxyl groups.

Journal ArticleDOI
TL;DR: The O-acetylserine sulfhydrylase associated with serine transacetylase in the complex appears to be identical with the previously described free O- acetyl-serine sulphhydryLase.

Journal ArticleDOI
TL;DR: Equilibrium sedimentation studies on native and carboxymethylated enzyme, analytical polyacrylamide disc gel electrophoresis in urea, pyridoxal phosphate analysis, tryptic peptide mapping, and amino acid analysis have shown that O-acetylserine sulfhydrylase-A consists of two identical subunits of molecular weight 34,000.

Journal ArticleDOI
TL;DR: This finding suggests that R-factors continue to replicate for several hours during the stationary phase of growth, which is consistent with a model in which individual copies of the R-factor are selected at random for replication without discrimination as to whether any particular copy has been duplicated one or more times during that generation.

Journal ArticleDOI
TL;DR: X-ray analysis of sperm whale myoglobin at 2·0 Å resolution provided the first solution of the structure of a protein, which consists of only one polypeptide chain of 153 residues and a single haem.
Abstract: Haemoglobin is the respiratory protein of the red blood cells which carries oxygen from the lungs to the tissues and facilitates, both directly and indirectly, the return transport of carbon dioxide. Mammalian haemoglobin has a molecular weight of 64500 and contains two pairs of polypeptide chains: the α -chains with 141 amino acid residues each and the β -chains with 146. Each chain is combined with one haem. Myoglobin, the oxygen carrier of muscle, is closely related to haemoglobin, but has a simpler constitution: it consists of only one polypeptide chain of 153 residues and a single haem. The amino acid sequences of the myoglobins and haemoglobins of man and of several animals have been determined (Dayhoff & Eck 1968). By means of the method of isomorphous replacement with heavy atoms, X-ray analysis of sperm whale myoglobin at 2·0 A resolution provided the first solution of the structure of a protein (Kendrew et al . 1960; Watson 1969). All but 21 of its 153 residues form part of helices; over most of their length these helices have conformations closely resembling the right-handed α -helix of Pauling & Corey (1951). The chain is divided into 8 helical segments, separated by corners or non-helical regions. Together these form a kind of basket into which the haem group fits neatly, so that only its propionic acid side-chains protrude into the surrounding liquid (figures 1, 2). X-ray analysis at 5·5 A resolution showed each chain of horse haemoglobin to be folded in much the same way as the single chain of sperm whale myoglobin. The 4 chains are arranged tetrahedrally, each carrying one haem in a pocket near the protein surface. The chemically identical halves of the molecule are related by a twofold symmetry axis (figure 3, plate 18; Cullis et al . 1962).

Journal ArticleDOI
TL;DR: The sequence of this tRNA is studied but certain results are in conflict with the above sequence but the sequences of the nucleotides are tentatively identified as 2-thiomethyl&isopentenyl adenylic acid.

Journal ArticleDOI
TL;DR: In this article, the origin of the grain boundary precipitate free zone is discussed in relation to Al-Zn-Mg and Al-Cu alloys using the occurrence of homogeneously distributed precipitate as a semi-quantitative indication of the excess vacancy concentration and its variation in the quenched alloys.

Journal ArticleDOI
11 Jan 1969-Nature
TL;DR: In the following three articles, details are given of the structure and chemical typing of immunoglobulins.
Abstract: In the following three articles, details are given of the structure and chemical typing of immunoglobulins.

Journal ArticleDOI
19 Apr 1969-Nature
TL;DR: The nucleotide sequence of tRNAVal1 is reported, comprising about 80 per cent of the total valine acceptor activity, and is coded by GUA and GUG, and the minor, t RNAVal2, by GUU and GUC.
Abstract: E. coli tRNA contains at least two valyl tRNAs. The major, tRNAVal1, comprising about 80 per cent of the total valine acceptor activity, is coded by GUA and GUG, and the minor, tRNAVal2, by GUU and GUC (ref. 1 and unpublished results of M. Y. and Rudland). We report here the nucleotide sequence of tRNAVal1.

Journal ArticleDOI
29 Mar 1969-Nature
TL;DR: An RNA species with properties suggesting that it is a messenger for haemoglobin synthesis has been purified from rabbit reticulocytes and resembles messenger RNA in its molecular size, its sensitivity to ribonuclease, its kinetics of in vivo labelling and the fingerprint obtained from its T1-rib onuclease digest.
Abstract: An RNA species with properties suggesting that it is a messenger for haemoglobin synthesis has been purified from rabbit reticulocytes. It resembles messenger RNA in its molecular size, its sensitivity to ribonuclease, its kinetics of in vivo labelling and the fingerprint obtained from its T1-ribonuclease digest.

Journal ArticleDOI
TL;DR: In this paper, the early stages of grain boundary precipitation in two aluminium alloys, Al-6 %Zu-3 %Mg and Al-7 % Mg, have been examined by transmission electron microscopy, and are discussed in relation to the heat treatment procedure and the properties of individual boundaries.

Journal ArticleDOI
27 Sep 1969-Nature
TL;DR: These two letters describe the interaction between two non-adjacent residues in tRNAVal1 at position eight and thirteen, and a new model of the tRNA molecule that takes into account this restriction.
Abstract: These two letters describe the interaction between two non-adjacent residues in tRNAVal1 at position eight and thirteen, and a new model of the tRNA molecule that takes into account this restriction.

Journal ArticleDOI
TL;DR: The final preparation, which appeared to be over 95% homogeneous by ultracentrifugal and electrophoretic criteria, has twice the specific activity of the most active fraction previously reported.

Journal ArticleDOI
08 Nov 1969-Nature
TL;DR: The sequence of the first fifty-five residues of protein ZUC (γ3 subclass) is presented and a stretch of the myeloma protein KUP which includes the five interchain S—S bonds characteristic of IgG3 proteins7 is compared.
Abstract: HEAVY chain disease1,2 is characterized by the presence in serum and urine of a protein associated structurally with the Fc fragment of immunoglobulins3–7. These proteins are not extracellular degradation products and seem to contain segments that are not normal components of the Fc3. The presence of PCA-Val-Gln at the N-terminus of one of these (ZUC8) suggests that they could result from abnormalities of gene expression. We now present the sequence of the first fifty-five residues of protein ZUC (γ3 subclass) and compare it with a stretch of the myeloma protein KUP which includes the five interchain S—S bonds characteristic of IgG3 proteins7. It is in this stretch that the abnormality in protein ZUC could be defined.

Journal ArticleDOI
27 Sep 1969-Nature
TL;DR: MYOSIN from rabbit skeletal muscle contains low molecular weight proteins (light chains) as well as the two large polypeptide chains which comprise the bulk of the molecule.
Abstract: MYOSIN from rabbit skeletal muscle contains low molecular weight proteins (light chains) as well as the two large polypeptide chains which comprise the bulk of the molecule. Alkali treatment has been used1–4 to separate the light from the heavy chains, and they have been characterized by gel electrophoresis and in the ultracentrifuge. The molecular weights are still in dispute, being reported as 20,000 daltons2 and 32,000 daltons3, but the light chains give at least three bands on gel electrophoresis and these molecular weight determinations2,3 were made with the mixture.