[CSBi-events] CSBi Seminar Series event on Friday, November 4

[csbi-events@mit.edu]

Dear CSBi Community,

This note is being sent simply to remind you of the CSBi Seminar 
Series event on Friday, November 4.
We hope you can attend.  Thank you.

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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