Biomedical subjects

J H van Opheusden

Publications and source records attributed to J H van Opheusden.

3 recordsLinked to original sources

PubMed1990

Structure of Arc repressor in solution: evidence for a family of beta-sheet DNA-binding proteins.

The Arc repressor, which is involved in the switch between lysis and lysogeny of Salmonella bacteriophage P22, does not belong to any of the known classes of DNA-binding proteins. Mutagenesis studies show that the DNA-binding region is located in the 15 N-terminal amino-acid residues. We have now determined the three-dimensional structure of the Arc dimer from an extensive set of interproton-distance data obtained from 1H NMR spectroscopy. A priori, intra- and inter-monomer nuclear Overhauser effects (NOEs) cannot be distinguished for a symmetric dimer. But by using the homology with the Escherichia coli Met repressor we could interpret the NOEs unambiguously in an iterative structure refinement procedure. The final structure satisfies a large set of NOE constraints (1,352 for the dimer). It shows a strongly intertwined dimer, in which residues 8-14 of different monomers form an antiparallel beta-sheet. A model for the Arc repressor-operator complex can account for all available biochemical and genetic data. In this model two Arc dimers bind with their beta-sheet regions in successive major grooves on one side of the DNA helix, similar to the Met repressor interaction. Thus, Arc and Met repressors are members of the same family of proteins, which contain an antiparallel beta-sheet as the DNA-binding motif.

Amino Acid Sequence↗

PubMed1987

Fractional exponential decay of a membrane protein population due to capture by coated pits.

We consider the lateral diffusion of receptors, or other membrane proteins, in the outer membranes of certain cells, and their capture by coated pits. It is shown, for the case in which the coated pits are in fixed random positions, that the long-time decay of the total number of uncaptured proteins is of the fractional exponential form, N(t) = N0 exp [-square root of (t/tau)], and not of the pure exponential form, N(t) = N0 exp(-t/tau), which is usually assumed.

Coated Pits, Cell-Membrane↗

PubMed1984

Forward rate constants for receptor clusters. Variational methods for upper and lower bounds.

We are interested in the effect of receptor clustering on k+, the diffusion-limited forward rate constant for the binding of a ligand to a cell surface receptor. Here we estimate the reduction in k+ when receptors are clustered in various configurations. We obtain two alternative expressions for the flux of ligands into receptors distributed on a surface. Next we show through a variational principle that these provide both upper and lower bounds on the flux when evaluated for trial concentration functions which satisfy only the boundary conditions of the Laplace equation. We use an analogy with electrostatics to calculate rigorous bounds within approx. 10% of the exact result for a variety of planar clusters of hemispherical receptor sites. We also obtain an exact result for the flux into a spheroidal receptor and use this result to obtain bounds on the flux into certain receptor clusters.

Animals↗