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Fast-acting enzymes with 2 fingers: Protein structurally and dynamically explained
Date:12/19/2012

Researchers at the RUB and from the MPI Dortmund have uncovered the mechanism that switches off the cell transport regulating proteins. They were able to resolve in detail how the central switch protein Rab is down-regulated with two "protein fingers" by its interaction partners. The structural and dynamic data is reported by the researchers led by Prof. Dr. Klaus Gerwert (Chair of Biophysics, RUB) and Prof. Dr. Roger S. Goody (Max Planck Institute for Molecular Physiology, Dortmund, Germany) in the Online Early Edition of the journal PNAS. "Unlike in the cell growth protein Ras, which is regulated with only one 'finger', we have surprisingly found a two-finger switch-off mechanism in Rab. This throws a completely new light on the functioning of certain enzymes, the small GTPases, to which Rab belongs", Klaus Gerwert explains.

Switch proteins associated with various diseases

Unlike Ras proteins that regulate cell growth, Rab GTPases (also called Rab proteins) control various transport operations between different areas of a cell. If the transport system is disrupted, diseases such as obesity can occur. The Rab proteins work as a switch, just like the Ras proteins. In the "on" state, the high-energy molecule GTP is bound, in the "off" state, the lower-energy GDP. The cleavage of GTP to GDP is catalysed by the so-termed RabGAP proteins. In so doing, GTP is split into GDP and phosphate. The research team observed the underlying reaction in time and space for the first time with the highest possible atomic resolution.

First a snapshot, then a whole film

Using X-ray structure analysis, the researchers first determined the spatial structure of the protein complex. The data showed a finger of the amino acid arginine, and a second finger of glutamine. The arginine finger was already known from Ras. The glutamine finger is new and surprising. RabGAP penetrates into the GTP-binding pocket of Rab with both finger
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Contact: Klaus Gerwert
klaus.gerwert@bph.ruhr-uni-bochum.de
49-234-322-4461
Ruhr-University Bochum
Source:Eurekalert

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