Regensburg 2010 – scientific programme

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BP: Fachverband Biologische Physik

BP 32: Posters: Physics of Cells

BP 32.3: Poster

Thursday, March 25, 2010, 17:15–20:00, Poster B1

Elucidating the interaction of misfolded proteins with the quality control machinery in the endoplasmic reticulum — •Nina Malchus and Matthias Weiss — DKFZ, Heidelberg, Germany

A multitude of transmembrane proteins enter the endoplasmic reticulum (ER) as unfolded polypeptide chains. During their folding process they interact repetitively with the ER's quality control machinery. Here, we have used fluorescence correlation spectroscopy to probe these interactions for a prototypical transmembrane protein, tsO-45-G, in vivo [1]. While both, folded and unfolded tsO-45-G showed anomalous diffusion, the unfolded protein had a significantly stronger anomaly. This difference subsided when unfolded tsO-45-G was in a complex with its chaperone calnexin, or when a mutant form of tsO-45-G with only one glycan was used. Our experimental data and accompanying simulations suggest that the folding sensor of the quality control (UGT1) oligomerizes unfolded tsO-45-G, leading to a more anomalous/obstructed diffusion. In contrast, calnexin dissolves the oligomers, rendering unfolded tsO-45-G more mobile, and hence prevents poisoning of the ER. Additionally, we performed computer simulations to investigate the origin of the spread in the anomaly obtained from FCS experiments on membranes [2].

[1] N. Malchus & M. Weiss, submitted.

[2] N. Malchus & M. Weiss, J. Fluoresc., in press.