[CSBi-events] CSBi Speaker Series - Dr. Carla Mattos - 11/4/05

[csbi-events@mit.edu]

Dear CSBi Community,

You may want to note the upcoming CSBi Speaker Series seminar, on 
Friday, November 4, and join us if your schedule permits.  Thanks!
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Dr. Carla Mattos
North Carolina State University
Department of Molecular and Structural Biochemistry

Deciphering Binding Sites on Ras GTPases

Friday, November 4, 2005
Maclaurin Building (4-270)
3:00 - 4:00 p.m.
Light refreshments served.

Abstract
Details of the surface of the RasGTPase bound to the GTP analogue 
GppNHp are studied using two main approaches. The first is through a 
new crystal form of the protein that presents the switch regions in a 
very different conformation than observed in the previously published 
crystal forms. In our new structure the conformation of Switch I 
superimposes well with the structure observed in the Raps/Raf 
complex, while the canonical form shows Switch I in the conformation 
found in the Ras/RasGAP interaction. Both of these forms can be 
correlated with structures observed in solution by 31P NMR 
spectroscopy and can be identified by having Tyr 32 in a closed or 
open conformation respectively. Our structure reveals that Switch II, 
which adopts multiple conformations in solution, is found in a 
conformation not previously seen in Ras, but which is similar to the 
non-catalytic conformation of Ran-GTP stabilized by importin-beta. 
The structure of the Q61L oncogenic mutant in the new crystal form 
reveals a network of hydrophobic interactions where Leu61 is stacked 
against Tyr32 on one side and Tyr64 on the other. These interactions 
appear to stabilize a non-catalytic form of Ras-GppNHp and may be an 
important factor in the oncogenic phenotype of the Q61L mutant.
The second approach used to study the surface of Ras-GppNHp is called 
the Multiple Solvent Crystal Structures (MSCS) method. Crystals are 
crosslinked with gluteraldehyde and transferred to several distinct 
organic solvent solutions, resulting in a series of crystal 
structures that can be superimposed for analysis. Using this method 
we identify two putative sites of protein-protein interaction in Ras 
away from the Switch regions. The locations of these sites coincide 
with the clustering of conserved residues in the close family member 
Ral-GppNHp.

Host: Dr. Bruce Tidor
Department of Electrical Engineering
and Computer Science
and Biological Engineering
                                   
				Contact: Brenda Pepe, Biology, 
452-3885
http://csbi.mit.edu/

Sponsored by  CSBi
Annual CSBi Seminar Series in Computational and Systems Biology
The entire MIT Community is welcome at this event!
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