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Salman S Rogers - One of the best experts on this subject based on the ideXlab platform.

  • The mechanism of amyloid spherulite formation by Bovine Insulin.
    Biophysical journal, 2005
    Co-Authors: Salman S Rogers
    Abstract:

    The formation of amyloid-containing spherulite-like structures has been observed in some instances of amyloid diseases, as well as in amyloid fibril-containing solutions in vitro. In this article we describe the structure and kinetics of Bovine Insulin amyloid fibril spherulites formed in the presence and absence of different salts and at different salt concentrations. The general spherulite structure consists of radially oriented amyloid fibrils, as shown by optical microscopy and environmental scanning electron microscopy. In the center of each spherulite, a "core" of less regularly oriented material is observed, whose size decreases when the spherulites are formed in the presence of increasing concentrations of NaCl. Similarly, amyloid fibrils form faster in the presence of NaCl than in its absence. A smaller enhancement of the rate of formation with salt concentration is observed for spherulites. These data suggest that both amyloid fibril formation and random aggregation occur concurrently under the conditions tested. Changes in their relative rates result in the different-sized cores observed in the spherulites. This mechanism can be likened to that leading to the formation of spherulites of polyethylene, in agreement with observations that polypeptide chains under partially denaturing conditions can exhibit behavior not dissimilar to that of synthetic polymers.

Robert H Blessing - One of the best experts on this subject based on the ideXlab platform.

  • The structure of T6 Bovine Insulin.
    Acta crystallographica. Section D Biological crystallography, 2005
    Co-Authors: G David Smith, Walter A Pangborn, Robert H Blessing
    Abstract:

    Porcine Insulin differs in sequence from Bovine Insulin at residues A8 (Thr in porcine-->Ala in Bovine) and A10 (Ile in porcine-->Val in Bovine). The structure of T6 hexameric Bovine Insulin has been determined to 2.25 A resolution at room temperature and refined to a residual of 0.162. The structure of the independent dimer is nearly identical to the T6 porcine Insulin dimer: the mean displacement of all backbone atoms is 0.16 A, with the largest displacements occurring at AlaB30. Each of two independent zinc ions is octahedrally coordinated by three HisB10 side chains and three water molecules. As has been observed in both human and porcine Insulin, the GluB13 side chains are directed towards the center of the hexamer, where a short contact of 2.57 A occurs between two independent carboxyl O atoms, again suggesting the presence of a centered hydrogen bond. No significant displacements of backbone atoms or changes in conformation are observed at A8 or A10. Since there are no interhexamer hydrogen-bonded contacts involving A8 in either porcine or Bovine Insulin, the change in the identity of this residue appears to have little or no effect upon the packing of the hexamers in the unit cell. In contrast, the side chains of the three A10 residues in one trimer make van der Waals contacts with the A10 side chains in a translationally related hexamer. As a consequence of the loss of the C(delta1) atom from the isoleucine residue in porcine Insulin to produce valine in Bovine Insulin, there is a 0.36 A decrease in the distance between independent pairs of C(beta) atoms and a 0.24 A decrease in the c dimension of the unit cell. Thus, the net effect of the change in sequence at A10 is to strengthen the stabilizing hydrophobic interactions between hexamers.

  • The structure of T6 Bovine Insulin.
    Acta Crystallographica Section D Biological Crystallography, 2005
    Co-Authors: G David Smith, Walter A Pangborn, Robert H Blessing
    Abstract:

    Porcine Insulin differs in sequence from Bovine Insulin at residues A8 (Thr in porcine→Ala in Bovine) and A10 (Ile in porcine→Val in Bovine). The structure of T6 hexameric Bovine Insulin has been determined to 2.25 A resolution at room temperature and refined to a residual of 0.162. The structure of the independent dimer is nearly identical to the T6 porcine Insulin dimer: the mean displacement of all backbone atoms is 0.16 A, with the largest displacements occurring at AlaB30. Each of two independent zinc ions is octahedrally coordinated by three HisB10 side chains and three water molecules. As has been observed in both human and porcine Insulin, the GluB13 side chains are directed towards the center of the hexamer, where a short contact of 2.57 A occurs between two independent carboxyl O atoms, again suggesting the presence of a centered hydrogen bond. No significant displacements of backbone atoms or changes in conformation are observed at A8 or A10. Since there are no interhexamer hydrogen-bonded contacts involving A8 in either porcine or Bovine Insulin, the change in the identity of this residue appears to have little or no effect upon the packing of the hexamers in the unit cell. In contrast, the side chains of the three A10 residues in one trimer make van der Waals contacts with the A10 side chains in a translationally related hexamer. As a consequence of the loss of the Cδ1 atom from the isoleucine residue in porcine Insulin to produce valine in Bovine Insulin, there is a 0.36 A decrease in the distance between independent pairs of Cβ atoms and a 0.24 A decrease in the c dimension of the unit cell. Thus, the net effect of the change in sequence at A10 is to strengthen the stabilizing hydrophobic interactions between hexamers.

Athene M. Donald - One of the best experts on this subject based on the ideXlab platform.

  • The formation of spherulites by amyloid fibrils of Bovine Insulin.
    Proceedings of the National Academy of Sciences of the United States of America, 2004
    Co-Authors: Mark R.h. Krebs, Cait E. Macphee, Aline F. Miller, Iain E. Dunlop, Christopher M. Dobson, Athene M. Donald
    Abstract:

    Bovine Insulin has long been known to self-assemble in vitro into amyloid fibrils. We have observed a further higher-order self-association of the protein into spherical structures, with diameters typically around 50 μm but ranging from 10 to 150 μm. In a polarizing light microscope, these structures exhibit a “Maltese-cross” extinction pattern typical of spherulites. Spherical structures of a similar size distribution can be observed in the environmental scanning electron microscope, which also reveals the presence of significant amounts of water in the structures. The spherulites contain a large quantity of well defined amyloid fibrils, suggesting that they are formed at least in part as a consequence of the self-assembly of preformed fibrils. Similar structures also have been observed in the tissues of patients suffering from amyloid disorders. The ability of amyloid fibrils to form such higher-order assemblies supports the hypothesis that they represent a generic form of polypeptide structure with properties that are analogous to those of classical synthetic polymers.

G David Smith - One of the best experts on this subject based on the ideXlab platform.

  • The structure of T6 Bovine Insulin.
    Acta crystallographica. Section D Biological crystallography, 2005
    Co-Authors: G David Smith, Walter A Pangborn, Robert H Blessing
    Abstract:

    Porcine Insulin differs in sequence from Bovine Insulin at residues A8 (Thr in porcine-->Ala in Bovine) and A10 (Ile in porcine-->Val in Bovine). The structure of T6 hexameric Bovine Insulin has been determined to 2.25 A resolution at room temperature and refined to a residual of 0.162. The structure of the independent dimer is nearly identical to the T6 porcine Insulin dimer: the mean displacement of all backbone atoms is 0.16 A, with the largest displacements occurring at AlaB30. Each of two independent zinc ions is octahedrally coordinated by three HisB10 side chains and three water molecules. As has been observed in both human and porcine Insulin, the GluB13 side chains are directed towards the center of the hexamer, where a short contact of 2.57 A occurs between two independent carboxyl O atoms, again suggesting the presence of a centered hydrogen bond. No significant displacements of backbone atoms or changes in conformation are observed at A8 or A10. Since there are no interhexamer hydrogen-bonded contacts involving A8 in either porcine or Bovine Insulin, the change in the identity of this residue appears to have little or no effect upon the packing of the hexamers in the unit cell. In contrast, the side chains of the three A10 residues in one trimer make van der Waals contacts with the A10 side chains in a translationally related hexamer. As a consequence of the loss of the C(delta1) atom from the isoleucine residue in porcine Insulin to produce valine in Bovine Insulin, there is a 0.36 A decrease in the distance between independent pairs of C(beta) atoms and a 0.24 A decrease in the c dimension of the unit cell. Thus, the net effect of the change in sequence at A10 is to strengthen the stabilizing hydrophobic interactions between hexamers.

  • The structure of T6 Bovine Insulin.
    Acta Crystallographica Section D Biological Crystallography, 2005
    Co-Authors: G David Smith, Walter A Pangborn, Robert H Blessing
    Abstract:

    Porcine Insulin differs in sequence from Bovine Insulin at residues A8 (Thr in porcine→Ala in Bovine) and A10 (Ile in porcine→Val in Bovine). The structure of T6 hexameric Bovine Insulin has been determined to 2.25 A resolution at room temperature and refined to a residual of 0.162. The structure of the independent dimer is nearly identical to the T6 porcine Insulin dimer: the mean displacement of all backbone atoms is 0.16 A, with the largest displacements occurring at AlaB30. Each of two independent zinc ions is octahedrally coordinated by three HisB10 side chains and three water molecules. As has been observed in both human and porcine Insulin, the GluB13 side chains are directed towards the center of the hexamer, where a short contact of 2.57 A occurs between two independent carboxyl O atoms, again suggesting the presence of a centered hydrogen bond. No significant displacements of backbone atoms or changes in conformation are observed at A8 or A10. Since there are no interhexamer hydrogen-bonded contacts involving A8 in either porcine or Bovine Insulin, the change in the identity of this residue appears to have little or no effect upon the packing of the hexamers in the unit cell. In contrast, the side chains of the three A10 residues in one trimer make van der Waals contacts with the A10 side chains in a translationally related hexamer. As a consequence of the loss of the Cδ1 atom from the isoleucine residue in porcine Insulin to produce valine in Bovine Insulin, there is a 0.36 A decrease in the distance between independent pairs of Cβ atoms and a 0.24 A decrease in the c dimension of the unit cell. Thus, the net effect of the change in sequence at A10 is to strengthen the stabilizing hydrophobic interactions between hexamers.

Mark R.h. Krebs - One of the best experts on this subject based on the ideXlab platform.

  • The formation of spherulites by amyloid fibrils of Bovine Insulin.
    Proceedings of the National Academy of Sciences of the United States of America, 2004
    Co-Authors: Mark R.h. Krebs, Cait E. Macphee, Aline F. Miller, Iain E. Dunlop, Christopher M. Dobson, Athene M. Donald
    Abstract:

    Bovine Insulin has long been known to self-assemble in vitro into amyloid fibrils. We have observed a further higher-order self-association of the protein into spherical structures, with diameters typically around 50 μm but ranging from 10 to 150 μm. In a polarizing light microscope, these structures exhibit a “Maltese-cross” extinction pattern typical of spherulites. Spherical structures of a similar size distribution can be observed in the environmental scanning electron microscope, which also reveals the presence of significant amounts of water in the structures. The spherulites contain a large quantity of well defined amyloid fibrils, suggesting that they are formed at least in part as a consequence of the self-assembly of preformed fibrils. Similar structures also have been observed in the tissues of patients suffering from amyloid disorders. The ability of amyloid fibrils to form such higher-order assemblies supports the hypothesis that they represent a generic form of polypeptide structure with properties that are analogous to those of classical synthetic polymers.