Biomedical subjects

K Prat

Publications and source records attributed to K Prat.

3 recordsLinked to original sources

PubMed2002

Structural features of prions explored by sequence analysis I. Sequence data.

Animal prion proteins (PrPs) form at the sequence level a very homogenous and 'closed' family. Therefore, few of their structural and functional features can be gleaned from sequence comparison as is now possible on a wide scale for other protein families. To detect putatively related proteins (at the structural and/or functional level), we used a battery of sequence analysis tools. This analysis resulted in (i) the identification of a putative 'prion-like' domain within the envelope of foamy retroviruses, (ii) the detection of putative similarities between prions and an interferon-inducible membrane protein, and (iii) the proposal that of the TATA-box-binding protein is a structural scaffold, which might allow understanding of a key event leading to the structural conversion from PrP(C) (normal cellular prion structure) towards PrP(Sc) (pathogenic structure).

Amino Acid Sequence↗

PubMed2002

Structural features of prions explored by sequence analysis. II. A PrP(Sc) model.

Prion diseases are neurodegenerative disorders associated with a conformational conversion of the prion PrP protein, in which the beta strand content increases and that of the a helix decreases. However, the structure of the pathogenous form PrP(Sc), occurring after conformational conversion of the normal cellular form PrP(C), is not yet known. From sequence analysis, we have previously proposed that helix H2 of the prion PrP(C) structure might be a key region for this structural conversion. More recently, we identified the TATA box-binding protein fold as a putative scaffold that may locally satisfy the predicted secondary-structure organisation of PrP(Sc). In the present analysis, we detail the schematic construction of PrP(Sc) monomeric and dimeric models, based on this hypothesis. These models are globally compatible with available data and therefore may provide further insights into the structurally and functionally elusive PrP protein. Some comments are also devoted to a comparison of the yeast Ure2p prion and animal prions.

Amino Acid Sequence↗

PubMed2001

Lens crystallins and oxidation: the special case of gammaS.

Among lens crystallins, gamma-crystallins are particularly sensitive to oxidation, because of their high amount of Cys and Met residues. They have the reputation to induce, upon ageing, lens structural modifications leading to opacities. A combination of small angle X-ray scattering and chromatography was used to study the oxidation of gamma-crystallins. At pH 7.0, all the gamma-crystallins under study were checked to have the same structure in solution. Under gentle oxidation conditions at pH 8.0, human gammaS (hgammaS) and bovine gammaS (bgammaS) formed disulfide-linked dimers, whereas the other bgamma-crystallins did not. Cys20 was shown to be responsible for dimer formation since the C20S mutant only formed monomers. The hgammaS dimers were stable for weeks and did not form higher oligomers. In contrast, monomeric gammaS-crystallins freshly prepared at pH 8.0, and submitted to more drastic oxidation by X-ray induced free radicals, were rapidly transformed into higher oligomers. So, only extensive oxidation causing partial unfolding could be detrimental to the lens and linked to cataract formation. The gammaS-crystallins lack the temperature-induced opacification observed with the other gamma-crystallins and known as cold cataract. The oxidation-induced associative behaviour and cold cataract are therefore demonstrated to be uncoupled.

Amino Acid Sequence↗