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IPLS/BioP Seminar - Prof. Edward Lemke (EMBL Heidelberg/IMB Mainz)

31 October 2018, 10:00 am–11:00 am

Prof. Edward Lemke

Decoding Molecular Plasticity in the Dark Proteome

Event Information

Open to

All

Availability

Yes

Organiser

Jas Gill-Thind

Location

2nd Floor Seminar Room
MRC Building, LMCB
UCL
London
WC1E 6BT
United Kingdom

Abstract: The mechanisms by which intrinsically disordered proteins (IDPs) engage in rapid and highly selective binding is a subject of considerable interest and represents a central paradigm to nuclear pore complex (NPC) function, where nuclear transport receptors (NTRs) move through the NPC by binding disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). In the first part of my talk, I will present a combined single molecule, microfluidic, ensemble spectroscopy, solvation approach that paired with atomic simulations reveals that a rapidly fluctuating FG-Nup populates an ensemble of conformations that are prone to bind NTRs with diffusion-limited on-rates. This is achieved using multiple, minimalistic, low affinity binding motifs that are in rapid exchange when engaging with the NTR, allowing the FG-Nup to maintain an unexpectedly high plasticity in its bound state. Since site-specific labeling of proteins with small but highly photostable fluorescent dyes inside cells remains the major bottleneck for directly performing such high-resolution studies in the interior of the cell, I will demonstrate an approach how to overcome this limitation in the second part of my talk. We have now developed a semi-synthetic strategy based on novel artificial amino acids that are easily and site-specifically introduced into any protein by the natural machinery of the living cell. Expressed proteins only differ from their natural counterparts by very few atoms, constituting a ring-strained cyclooctyne or cyclooctene functional group. This allowed rapid, specific “click” labeling and even multi-color studies of living cells and subsequent super resolution microscopy.

About the Speaker

Prof. Edward Lemke

at EMBL Heidelberg/IMB Mainz

More about Prof. Edward Lemke