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Biomedical subjects

G N Phillips

Publications and source records attributed to G N Phillips.

84 records · Page 5Linked to original sources
PubMed1981

Streptococcal M protein: alpha-helical coiled-coil structure and arrangement on the cell surface.

The conformation and molecular dimensions of purified type 6 streptococcal M proteins establish the close structural relationship of these molecules to tropomyosin. Ultracentrifuge studies reveal that the M molecules exist as stable dimers; circular dichroism spectra indicate that the molecules contain about 70% alpha helix; and fiber x-ray diffraction diagrams show the characteristic reflections of the alpha-helical pattern. Electron microscopic images of M protein shadowed with platinum reveal rod-shaped molecules having the same width as tropomyosin. However, the lengths of the M molecules are about 30% shorter than lengths predicted by assuming a completely alpha-helical molecule. These findings indicate that the structure of the M6 protein is primarily alpha-helical coiled coil. Comparison of the lengths of the fibers on the surface of the streptococcus and the isolated M proteins suggests that each fiber on the cell wall consists of a single M-protein molecule approximately 500 A long. The structure determined for these fimbriae is the first alpha-helical coiled-coil conformation to be demonstrated for bacterial surface projections.

Antibodies, Bacterial↗
PubMed1981

Spikes and fimbriae: alpha-helical proteins form surface projections on microorganisms.

Two basic alpha-helical plans appear to characterize portions of the proteins projecting from the surface of many microorganisms. Structure A is related to that of the antibody-binding protein A of Staphylococcus aureus, in which a single polypeptide chain doubles back to form an Anti-parallel domain; the other, structure M, is related to the M proteins of group A streptococci, in which Multiple parallel alpha-helical chains interlock in a coiled-coil conformation. A projection about 100 A long may be organized on either plan, but very long projections are likely to be of the M pattern. The alpha-helical motif may account for the length of these spikes, with other functions such as anchoring or antiphagocytic activity located in domains of different structure.

Bacterial Proteins↗
PubMed1980

Motions of tropomyosin. Crystal as metaphor.

Movements of tropomyosin play an essential role in muscle regulation. This fibrous protein is a two-chain alpha-helical coiled coil that bonds head to tail to form cables wound in the two long grooves of the actin helix. The regulatory switch consists of tropomyosin and a "globular" Ca2+-sensitive protein complex called troponin. The structure of the tropomyosin filaments has now been determined by x-ray crystallography to approximately 15 A resolution. The complete sequence of alpha-tropomyosin is known; by using mercury markers on the cysteine residues the ends of the molecules in the filaments have been identified. Details of the coiled-coil structure have also been visualized by refinement of models against the diffraction data. The average pitch of the coiled coil is approximately 137 A, so that each tropomyosin molecule can make similar contacts with seven actin monomers. The electron density map also indicates that departures from the alpha-helical coiled coil occur in a few localized regions of the molecule, especially at the overlapping ends. Motions of tropomyosin in the crystal lattice are displaced by the character of the Bragg reflections and the strong diffuse scatter. These effects depend markedly on temperature. It appears that the molecular filaments fluctuate freely in a direction perpendicular to their axes. Moreover, the C-terminal half of the molecule "unfolds" to some degree at less than physiological temperatures. Crystallographic results on co-crystals of tropomyosin and a component of troponin (TnT) suggest that this subunit consists of structurally distinct domains, so that the troponin complex is not in fact simply "globular". The interactions of the extended alpha-helical region of TnT may "stiffen" tropomyosin and influence its motions. We picture the tropomyosin/troponin switch in muscle as a restless cable, perpetually making and breaking bonds as it vibrates on the thin filament. These movements of tropomyosin probably depend on two aspects of its design: the regular pattern of coiled-coil linkages with actin; and the aperiodic features that allow flexibility and motion.

Animals↗
PubMed1980

Protein switches in muscle contraction.

Two types of Ca2+-sensitive protein complexes control the contraction of muscle: Troponin (TN) and tropomyosin (TM) are associated with the thin actin filaments, and a specific light chain is a regulatory subunit of myosin itself. Most muscles have both types of regulation. X-ray diffraction diagrams from whole muscle have shown changes in the position of tropomyosin and changes in the pattern of myosin crossbridge attachment associated with different states of the regulatory switches. The full interpretation of these diagrams is often ambiguous, however, and structural studies of the purified proteins provide essential information. Recent crystallographic results reveal that the TM molecule has unusual local domains of marginal stability, leading to extensive motions of the tropomyosin filaments. Electron microscopy of negatively stained thin filaments decorated with subfragments of scallop myosin yields unusually detailed images that show marked conformational changes in myosin crossbridges that are dependent on the presence or absence of the regulatory light chain. These observations suggest that both the special dynamic design of tropomyosin and the striking structural changes in the myosin crossbridges are significant clues for detailed models for the regulatory mechanism.

Actins↗
PubMed1979

Crystal structure and molecular interactions of tropomyosin.

The three-dimensional structure of tropomyosin filaments has been determined by X-ray crystallography. The ends of the molecules were located by reference to the single pair of cysteine residues. Departures from the alpha-helical-coiled coil conformation may occur in localised domains along the molecule as well as at the overlapping ends.

Amino Acid Sequence↗
PubMed1978

The Klippel-Trenaunay syndrome: clinical and radiological aspects.

Klippel-Trenaunay syndrome (KTS) is characterized by port-wine hemangiomas, deep venous system abnormalities, superficial varicosities, and bony and soft-tissue hypertrophy. When associated with an arteriovenous fistula, it has been termed Klippel-Trenaunay-Parkes-Weber syndrome. It is imperative that both the radiologist and surgeon be aware of this entity, as incomplete evaluation and inappropriate surgery may be devastating. Radiological workup includes phlebography, angiography, and conventional radiography of the involved extremities. Surgery should be performed only to relieve deep venous obstruction (if present) or to correct inequality in the lengths of legs. Removal of superficial varicosities is contraindicated because it will worsen existing symptoms. Five cases of KTS are presented and the literature reviewed.

Adolescent↗
PubMed1976

Structure of L-arabinose-binding protein from Escherichia coli at 5 A resolution and preliminary results at 3.5 A.

The three-dimensional crystal structure of the L-arabinose-binding protein from E. coli, an essential component in the active transport of L-arabinose, has been solved at 5 A resolution using the method of multiple isomorphous replacement. Five heavy atom derivatives were used. A preliminary 3.5 A electron density map has also been calculated. The results indicate that the molecule is ellipsoidal with approximate dimensions 68 A X 38 A X 30 A. Two similar domains within the molecule (which is a single polypeptide chain) are related by an approximate noncrystallographic rotation-translation axis. This relationship involves approximately 20% of the structure.

Arabinose↗
PubMedDate not supplied

Preliminary electron crystallographic analysis of ice-embedded tropomyosin crystals.

Electron images and diffraction patterns of ice-embedded tropomyosin crystalline sheets have been recorded at 100 and 400 kV. Optical diffractograms from the images indicated an elongated, centered unit cell with a = 799.2 +/- 10.6 A, b = 55.1 +/- 3.5 A. Evaluation of the phases in the computed Fourier transforms up to 7 A resolution revealed the presence of symmetry axes consistent with two-dimensional space group cmm. Electron diffraction patterns show diffuse arcs and discrete sampling at a resolution of 5.1 A, arising from the alpha-helical coiled-coil features of the molecule. These results demonstrate that tropomyosin thin sheets are highly ordered and suggest that retrieval of its high-resolution three-dimensional structure may be feasible by electron crystallography.

Animals↗
PubMedDate not supplied

Ultrasonic evaluation of the scrotum.

Ultrasonography has proved to be a highly useful method for detecting testicular lesions, correlating them with clinical findings, and indicating whether scrotal masses are caused by fluid or by solid tissue. It has not been possible, however, to distinguish spermatic cord torsion from epididymitis.

Cysts↗
PubMedDate not supplied

Structure of co-crystals of tropomyosin and troponin.

Troponin, a Ca2+-sensitive complex, regulates the motions of tropomyosin on the thin filaments in many muscles. It has three subunits, each with a different architecture and function: TnC binds Ca2+; TnI binds to actin and inhibits contraction; and TnT binds one complex to each tropomyosin molecule. The troponin complex has an elongated shape with TnC and TnI forming a globular 'head' region and TnT a long (approximately 160 A) 'tail'. TnT binds to two widely separated regions of tropomyosin: the head region of the complex is near Cys 190 of tropomyosin and the tail region is near the overlapping joint that links the tropomyosin molecules into filaments. Here we report the X-ray structure determination at 17 A resolution of glutaraldehyde-treated tropomyosin crystals in which native troponin complex or fragments of TnT have been bound. Our results show that the amino-terminal tail end of TnT spans the head-to-tail joint of the tropomyosin filaments, and that the 'head' region of the whole troponin complex binds approximately 200 A away near residues 150-180 of the tropomyosin molecule.

Animals↗