International Symposium 2017

 Understanding Intramembrane Proteolysis

 From Substrates to Enzymes



 

Topics of the International Symposium 2017:

 

  • Structure, Dynamics and Function of Intramembrane Proteases and their Substrates
  • Membrane-Associated Proteases in Functional Networks

  

Membrane-associated sheddases frequently cooperate with intramembrane proteases in substrate processing. The common functional denominator of intramembrane proteases is cleavage within the plane of the membrane, which usually results in peptide bond scission within the transmembrane helices of their substrates. The functional consequences of intramembrane proteolysis include activation of membrane-tethered transcription factors, secretion of growth factors, maturation of a bacterial translocation channel, and regulated protein degradation. The malfunction of intramembrane proteases can lead to Alzheimer’s disease, frontotemporal lobe degeneration, Parkinson’s disease, type-2 diabetes, glaucoma, and certain cancers. Although different families of intramembrane proteases have been discovered and despite recent progress in the determination of high-resolution structures, it is still unknown how these enzymes distinguish between substrates and non-substrates. Therefore, much effort is currently directed at determining the mechanisms of substrate recognition and cleavage.

 

This symposium brings together biochemistry, cell biology, biophysics, proteomics, bioinformatics, and molecular modelling and focuses on the biology and the molecular mechanism of substrate processing by different types of membrane-associated proteases.

 

Program


Wednesday, October 4th:


 

14:00

Check-in & Registration

 

 

15:00

Welcome & Introduktion

Dieter Langosch and Harald Steiner

 

 

Keynote lecture:

 

15:15

What Lurks Beneath (the Membrane): A Mechanistic Exploration of Rhomboid Proteolysis”

Siniša Urban (Johns Hopkins University, Baltimore)

 

 

16:15

Coffee break

 

 

Session 1: Rhomboid Proteases

Chair: Christian Haass

 

16:45

Making the Cut: Regulation of Mitochondrial PARL Intramembrane Proteolysis and its Implications in Parkinson's Disease

Joanne Lemieux (University of Alberta)

 

 

17:15

"Chemical Tools for the Study of Rhomboid Proteases"

Steven Verhelst (KU Leuven)

 

 

17:45

“Unwinding of the Substrate Transmembrane Helix in Intramembrane Proteolysis”

Iban Ubarretxena-Belandia (Icahn School of Medicine, New York)

 

 

18:00

Rhomboid Proteases: from Substrates to Inhibitors to Functions”

Kvido Stříšovský (CAS, Prague)

 

 

18:30

"Differential Membrane Proteomics Identifies ERAD-R Substrates of Signal Peptide Peptidase"

Marius Lemberg (ZMBH, Heidelberg)

 

 

19:30

Dinner

 


Thursday, October 5th:


 

Session 2: Aspartyl- and Metalloproteases I

Chairs: Marius Lemberg, Stefan Lichtenthaler

 

9:00

Structural and Functional Investigations of Human γ-Secretase

Linfeng Sun (Tsinghua University, Beijing)

 

 

09:30

„Molecular Simulation Analysis of γ-secretase Dynamics and Substrate Binding”

Martin Zacharias (TU Munich)

 

 

09:50

„New Insights into Substrate Binding of γ-secretase”

Harald Steiner (LMU & DZNE Munich)

 

 

10:10

“β- and γ-Secretases in Alzheimer’s Disease: How Do we Specifically Target their Pathological Roles?“

Lawrence Rajendran (University of Zurich)

 

 

10:40

„Mechanism of Substrate Recognition by the Exosites in γ-secretase”

Akio Fukumori (Osaka University)

 

 

10:55

Coffee Break

 

 

 

11:25

Dissecting Substrate/Enzyme Interaction in Intramembrane Proteolysis"

Dieter Langosch (TU Munich)

 

 

11:45

Molecular Dynamics of the Transmembrane Segments of Target Proteins for Intramembrane Proteolysis

Daniel Huster (University of Leipzig)

 

 

12:05

“Investigation of Structure and Dynamics of APP Transmembrane α-Helix by Solution State NMR Spectroscopy”

Burkhard Luy (KIT, Karlsruhe)

 

 

12:25

Comparing Conformational Dynamics of γ-Secretase Substrates Using a Multi-Scale Molecular Dynamics Approach”

Christina Scharnagl (TU Munich)

 

 

12:45

“SREBP: Bending Dynamics of the S2P Substrate”

Rasmus Linser (TU Munich)

 

 

13:00

Lunch & Recreation

 

 

14:15

Leaving the hotel for a short river cruise

(anyone who wants to come)

 

14:30

Historical “Strudel”-Roundtrip; 45 min Sightseeing on board of the MS Bruckmadl (8,90€);

 

 

 

 

Session 3: Proteases in Functional Networks

 

Chair: Regina Fluhrer

 

 

17:00

“Harnessing Membrane Proteases to Reverse Tissue Fibrosis “

 

Irit Sagi (Weizmann Institute, Rehovot)

 

 

17:30

„Gatekeeping and Quality Control during Fertilization by Ovastacin and Fetuin-B at the Egg Surface”

 

Walter Stöcker (JGU, Mainz)

 

 

18:00

„Intramembranous Processing by γ-Secretase Regulates Reverse Signaling of Ephrin-B2 in Migration of Microglia”

 

Jochen Walter (University of Bonn)

 

 

18:15

"TREM2 - from Microglial Dysfunction to Human Patients"

 

Christian Haass (LMU & DZNE Munich)

 

 

18:35

Poster Flash talks

 

 

 

 

19:00

Dinner

 

 

Session 4: Poster-Session

Hotel Lobby

 


Friday, October 6th:


 

Session 5: Aspartyl- and Metalloproteases II

 

Chairs: Harald Steiner, Dieter Langosch

 

 

9:00

"ADAM17 at the Control of Inflammation and Cancer”

 

Stefan Rose-John (University of Kiel)

   

09:30

 

“γ-Secretase and the Mechanism of Alzheimer’s Disease”

 

Michael Wolfe (University of Kansas)

 

 

10:00

Alzheimer’s Disease causing Mutations prime γ-Secretase - APP/Aβn interactions for dissociation

 

Lucia Chávez‐Gutiérrez (KU Leuven)

 

 

10:30

“ß-Sheet Structure within the Extracellular Domain of C99 Regulates Amyloidogenic Processing by γ-Secretase"

 

Steven O. Smith (Stony Brook University, New York)

 

 

11:00

Coffee Break

 

 

 

11:30

“Mechanism and Function of Naturally Short γ-Secretase Substrates"

 

Stefan Lichtenthaler (TUM & DZNE Munich)

 

 

11:50

"Signal Peptide Peptidase-Like Intramembrane Proteases - from Function to Pathophysiology"

 

Bernd Schröder (University of Kiel)

 

 

12:10

“Substrate Recognition Strategies of Signal Peptide Peptidase-like Proteases “

 

Regina Fluhrer (LMU & DZNE Munich)

 

 

13:00

Lunch & Departure

 

 


Download the final program of the UIP Symposium 2017  (PDF)

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