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Biomedical subjects

H Appel

Publications and source records attributed to H Appel.

9 recordsLinked to original sources

X-ray solution scattering reveals conformational changes upon iron uptake in lactoferrin, serum and ovo-transferrins.

X-ray solution scattering has been used for studying the structural changes that take place upon uptake and release of iron from serum and chicken ovo-transferrin and human lactoferrin. In the case of chicken ovo-transferrin, data have been obtained for both the intact protein and the isolated N and C-lobes with and without iron. These studies reveal that both lobes undergo a change that is consistent with an opening of the inter-domain cleft when iron is removed from the protein. We suggest that the conformational change of the protein increases the specificity of receptor binding and that the closed configuration of the iron-loaded protein is one, or perhaps the, decisive step in the mechanism for receptor-mediated endocytosis.

Animals

Influence of protein dynamics on the metal-sites of ovotransferrin.

Using the perturbed angular correlations (PAC) technique, the formation of hafnium-ovotransferrin complexes has been studied. Two binding configurations at each of the two specific binding-sites of the protein have been observed. They are characterized by well-defined electric quadrupole frequencies. Information about the dynamics of the protein was derived from temperature dependent measurements of the relaxation constant. The well-resolved spectra taken with fast BaF2-detectors allow a precise determination of the relaxation behaviour of the protein. The results are compared with the predictions from a hydrodynamic model for the reorientation of macromolecules. Thus the hydrodynamic volume of ovotransferrin and its N-terminal half-molecule were determined. The ovotransferrin volume is in agreement with a value derived for human serum transferrin from small angle neutron scattering. From experiments with immobilized protein material there is evidence for internal protein dynamics which is probed by the Hf-ion bound to the specific metal-sites.

Animals

TDPAC studies of the metal-binding sites in serum transferrin: comparison between 181Hf-labeled human- and rat-serum transferrin.

The binding of hafnium to human serum transferrin was studied using the time differential perturbed angular correlation (TDPAC-) technique. The samples were prepared in vitro by adding 181Hf-NTA solution to human serum. Two specific electric quadrupole interactions were observed, which correspond to two well-defined binding configurations. Their relative intensities depend on the pH, salt- and hafnium-concentrations, and on the incubation time. The present data may be compared with the results of a previous rat serum study, where the hafnium binding to transferrin behaved rather similarly. Small but significant differences, however, can be deduced from the TDPAC-parameters for these human and rat transferrin species. For either binding configuration, the electric field gradient (EFG) is slightly higher in the case of rat transferrin. The most characteristic difference, however, concerns the asymmetry parameter eta 2 of the second binding configuration, which is about 10% smaller for rat serum transferrin. The TDPAC-technique might be used as a sensitive and reliable analytical method to study the metal-binding sites of different transferrin species.

Animals

A hydrogen bond study in tobacco mosaic virus using Moessbauer spectroscopy.

The Moessbauer method was applied to obtain information on a suggested hydrogen bond in tobacco mosaic virus (TMV), between the hydroxyl group of Tyr 139 and a carboxyl oxygen of Glu 22 in a neighbouring subunit. Spectra of 129I were taken of 3,5-di-iodo-L-tyrosine as a free amino acid and in situ in TMV. The increase of the pK value of 3,5-di-iodo-L-tyrosine by 0.8 units at position 139 in TMV compared to the free value is a strong argument in favour of the existence of a hydrogen bond via the relevant hydroxyl group. The reported study demonstrates the surprising sensitivity of the observable Moessbauer parameters to details of the electronic configuration in the neighbourhood of the probe nucleus.

Biophysical Phenomena

In vivo and in vitro studies of hafnium-binding to rat serum transferrin.

The binding of hafnium to rat serum transferrin was studied using the time differential perturbed angular correlation (TDPAC) technique. Hafnium is interesting as a toxic metal binding to transferrin because it behaves metabolically similarly to plutonium. The isotope 181Hf offers favorable access to the TDPAC-method. Samples were prepared in vivo by intravenous injection of Hf-NTA, Hf-citrate, and Hf-oxalate solutions, respectively, into Sprague-Dawley rats and in vitro by adding Hf-NTA solution to fresh rat serum. In both cases two specific electric quadrupole interactions were observed, which correspond to two well-defined binding configurations. They may be attributed to the N-terminal and the C-terminal binding site in the transferrin molecule. The 181Hf-distribution between these two binding states depends on pH, salt and hafnium concentrations, temperature, and incubation time. With a fast TDPAC-setup of four BaF2-detectors a time resolution of about 600 ps could be achieved. The specific binding configurations of 181Hf and the comparatively slow relaxation times lead to spectra of considerable accuracy.

Animals

[Patterns of injuries of restrained car passengers (author's transl)].

A detailed analysis of actual traffic accidents involving car passengers wearing seat belts was carried out by an interdisciplinary team. The passengers were examined for the severity of their injuries, the combination of their injuries, and the practicality of their seat belt system. The type of injury to the car, the speed, and the line of impact were related to the injuries. Incorrect use of the belt system, malfunction due to external causes, and construction defects in the seat belt system were described and evaluated according to their specific importance.

Accidents, Traffic