Startseite Substrate processing in intramembrane proteolysis by γ-secretase – the role of protein dynamics
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Substrate processing in intramembrane proteolysis by γ-secretase – the role of protein dynamics

  • Dieter Langosch

    Dieter Langosch is interested in the structure and function of integral membrane proteins from the perspective of protein/protein recognition, onformational dynamics, and evolution. Within this wider framework, he investigates the mechanism of intramembrane proteolysis and biological membrane fusion.

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    und Harald Steiner

    Harald Steiner is interested in the biochemistry of gamma-secretase, a pivotal intramembrane protease and one of the key players in the generation of the amyloid-β peptide that is believed to be causative for Alzheimer’s disease.

Veröffentlicht/Copyright: 15. November 2016

Abstract

Intramembrane proteases comprise a number of different membrane proteins with different types of catalytic sites. Their common denominator is cleavage within the plane of the membrane, which usually results in peptide bond scission within the transmembrane helices of their substrates. Despite recent progress in the determination of high-resolution structures, as illustrated here for the γ-secretase complex and its substrate C99, it is still unknown how these enzymes function and how they distinguish between substrates and non-substrates. In principle, substrate/non-substrate discrimination could occur at the level of substrate binding and/or cleavage. Focusing on the γ-secretase/C99 pair, we will discuss recent observations suggesting that global motions within a substrate transmembrane helix may be much more important for defining a substrate than local unraveling at cleavage sites.

About the authors

Dieter Langosch

Dieter Langosch is interested in the structure and function of integral membrane proteins from the perspective of protein/protein recognition, onformational dynamics, and evolution. Within this wider framework, he investigates the mechanism of intramembrane proteolysis and biological membrane fusion.

Harald Steiner

Harald Steiner is interested in the biochemistry of gamma-secretase, a pivotal intramembrane protease and one of the key players in the generation of the amyloid-β peptide that is believed to be causative for Alzheimer’s disease.

Acknowledgements

This work was supported by grants LA699/14-1 (DL) as well as grants LA699/20-1 (DL) and STE847/4-1 (HS) within FOR 2290 of the Deutsche Forschungsgemeinschaft, by grant 01GI1004H of the Bundesministerium für Forschung und Technologie (KNDD), the State of Bavaria and the Center of Integrative Protein Science Munich (CIPSM) (DL).

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Received: 2016-8-17
Accepted: 2016-11-8
Published Online: 2016-11-15
Published in Print: 2017-4-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

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