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Transmembrane peptides from the receptor tyrosine kinase, ErbB-2, at high concentrations exhibit prominent spectra of rapidly rotating transmembrane monomers and slowly rotating large oligomers. At low concentration of the peptides, the oligomer spectra are diminished but a population of homodimers and/or small oligomers appears, suggesting the peptides possess interaction sites.

Val(super.659)-to-Glu mutation in the transmembrane domain of ErbB-2 has been studied with effects measured by (super.2)H NMR in fluid phospholipid bilayers. Results of the study could mean that the glutamic acid residue characterizing the mutant is not charged at neutral pH. Narrowed spectral components from species rotating rapidly and symmetrically in the membrane seem to be monomeric peptide. Evidence of effect at the upstream site at the membrane surface was almost nonexistent. The transforming mutation is likely associated with significant intramolecular rearrangement of the monomeric transmembrane helix, extending over some four helix turns, which could influence lateral associations. Temperature effects on spectral quadrupole splittings indicated greater peptide backbone flexibility of the wild-type transmembrane region.

Research has been conducted on receptor tyrosine kinase transmembrane domains. Expression, isolation and assembly of the transmembrane peptides into membranes are described.

A study relating to the investigation of the function of receptor tyrosine kinases was conducted to specifically scrutinize spectral data from three alamine residues within the putative transmembrane domain using H NMR spectroscopy. Experimental data strongly suggests that the peptide long axis tilts at an angle of between 10 and 14 degrees in fluid membranes of 1-palmitoyl-2-oleophosphatidylcholine (POPC) and between 10 and 12 degrees in POPC/cholesterol assuming that the transmembrane domain of the human EGF receptor is required to be a right-handed alpha-helix of 3.6 residues per turn.

A study was conducted to study the influence of phosphorylation on a threonine residue within the cytoplasmic domain of the human epidermal growth factor. A Varian Unity 500 spectrometer was utilized to determine 2H nuclear magnetic resonance spectra while study samples were prepared as unsonicated liposomes using a standard protocol. Results showed that protein phosphorylation supports several functions in biological systems.

The effect of the presence of the occluding loop on the endopeptidase activity of cathepsin B was investigated through using internally quenched fluorogenic (IQF) substrates. Results indicated that cathepsin B possessed high endopeptidase activity when the contacts between the loop and the enzyme were cleaved. The major increase in the endopeptidase activity was secondary to the increase in the loop flexibility.

Recognition of macromolecules by glycosphingolipids was thought to depend primarily on the nature of its carbohydrate component, and secondarily on the structure of the single fatty acid. The physical effect of a change in this single fatty acid was analyzed using altered deuterated globotriaosylceramide (Gb3). Long and short species of altered globosides were used to detect any change due to headgroup differences. The study showed that the changes in glycolipid receptor function associated with fatty acid variation resulted from a change in the fatty acid's thermodynamic interaction with the host matrix.

The first wide-line 2H NMR study of a receptor tyrosine kinase was conducted. Deuterized peptides from the membrane-associated segment of the human epidermal growth factor (EGF) receptor were synthesized for study in lipid bilayers mimicking certain natural membrane characteristics. In fluid membranes, peptide formation and orientation were noticeably insensitive to temperature and associated variations in lipid fluidity over a wide range. Addition of cholesterol decreased the rate of peptide axial diffusion at temperatures below the physiological level.

The binding of calcium induces a conformational change in the recombinant human brain calcium-binding protein S100b. This prompts the protein to interact with other proteins through its hydrophobic surface. The chemical shift changes for G19 and G22 in the site I Ca-binding loop of S100b are considerably similar to those for G18 and G57 in calbindin D(sub 9K). The cluster of hydrophobic residues includes F14, F73, and F88. This cluster probably plays an important role in the interactions of S100b with other proteins.

The effect of sialic acid on a membrane-localized oligosaccharide recognition site is investigated. Three glycosphingolipids with differing amounts of sialic acid are studied using wideline nuclear magnetic resonance spectroscopy. Results indicate surprisingly stable conformations of oligosaccharide recognition sites at membrane surfaces, despite the presence of sialic acid.

A 2H nuclear magnetic resonance study was conducted on the influence of ceramide fatty acids on the glycosphingolipid carbohydrate headgroup in fluid phospholipid bilayers. Observed spectra at given temperatures were nearly uniform for galactosylceramides dispersed in the fluid phase. The only spectral differences occured in the species with alpha-hydroxy-substituted fatty acids. The results indicate that only minute changes occur in the average glycosphingolipid carbohydrate headgroup orientation and in the smplitude of orientational fluctuations to the sphingosine backbone due to the nature of fatty acid attached to the sphingosine backbone.