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A Brünger

Publications and source records attributed to A Brünger.

6 recordsLinked to original sources
PubMed1990

Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins.

Ras proteins participate as a molecular switch in the early steps of the signal transduction pathway that is associated with cell growth and differentiation. When the protein is in its GTP complexed form it is active in signal transduction, whereas it is inactive in its GDP complexed form. A comparison of eight three-dimensional structures of ras proteins in four different crystal lattices, five with a nonhydrolyzable GTP analog and three with GDP, reveals that the "on" and "off" states of the switch are distinguished by conformational differences that span a length of more than 40 A, and are induced by the gamma-phosphate. The most significant differences are localized in two regions: residues 30 to 38 (the switch I region) in the second loop and residues 60 to 76 (the switch II region) consisting of the fourth loop and the short alpha-helix that follows the loop. Both regions are highly exposed and form a continuous strip on the molecular surface most likely to be the recognition sites for the effector and receptor molecule(or molecules). The conformational differences also provide a structural basis for understanding the biological and biochemical changes of the proteins due to oncogenic mutations, autophosphorylation, and GTP hydrolysis, and for understanding the interactions with other proteins.

Binding Sites↗
PubMed1988

Determination of the backbone conformation of secretin by restrained molecular dynamics on the basis of interproton distance data.

The backbone conformation of the 27-residue polypeptide hormone secretin has been investigated using nuclear magnetic resonance spectroscopy and restrained molecular dynamics calculations under conditions where it adopts a fully ordered structure (40% v/v trifluoroethanol). The basis for the restrained molecular dynamics calculations consists of 52 nuclear-Overhauser-enhancement-derived interproton distance restraints involving the NH, C alpha H and C beta H protons. It is shown that convergence to similar extended structures is achieved starting from four different initial structures, namely an alpha helix, a mixed alpha/beta structure, a beta strand and a polyproline helix. The converged structures are made up of short N- and C-terminal strand-like regions and a central region comprising two irregular helices connected by a 'half-turn'.

Energy Transfer↗
PubMed1981

Continuous fluorescence microphotolysis: A sensitive method for study of diffusion processes in single cells.

Continuous fluorescence microphotolysis is a sensitive method for the study of translational diffusion in the plasma membrane of single living cells and related systems. In this communication the conceptual basis of the method and its theoretical framework and experimental realization, as well as applications, are reported. In continuous fluorescence microphotolysis a microscopic membrane area of a single fluorescently labeled cell is irradiated by a laser beam while the fluorescence emitted from the area is monitored. The decay of the measuring signal reflects the competition of two processes: (i) the elimination of fluorophores by irreversible photolysis, and (ii) the entrance of new fluorophores into the area by diffusion. Rate constants for the two processes can be derived from the measuring data by mathematical analysis. As compared to our initial approach, fluorescence microphotolysis [Peters, R., Peters, J., Tews, K. H. & Bähr, W. (1974) Biochim. Biophys. Acta 367, 282-294], the main advantage of the method described here is an improvement of data quality and detection limit by orders of magnitude. From the practical point of view the main advantage is a simplification of the experimental setup. Results obtained by this method are encouraging and support the contention that continuous fluorescence microphotolysis may disclose new aspects of diffusion processes in biological systems.

Journal Article↗