The North Jersey ACS NMR Topical Group proudly presents its April monthly meeting at Princeton University on Wednesday, April 16, 2014. [ register ][raw]
VENUE: Please note the change in location for this meeting. The meeting will be at Princeton University, with the dinner in the Lobby of Frick Chemistry Building, and the seminar at Jadwin A06 (just across from the Chemistry Building)
“Early stages of protein folding and intrinsic disorder explored by NMR and hydrogen exchange”
Fox Chase Cancer Center, Philadelphia, PA 19111
6:00 pm Dinner
7:00 pm Seminar
NOTE CHANGE IN LOCATION FOR THIS MEETING
Princeton University, Princeton, NJ
Dinner – Lobby of Frick Chemistry Building
Seminar – Jadwin A06 (just across from the Chemistry Building)
Parking: Lot 21, see campus map
Dinner cost: $15 employed/ $5 for students, postdocs, retired and unemployed
No charge for seminar only
Register: Online below or via e-mail to Swapna Gurla at firstname.lastname@example.org.
My talk will focus on our recent applications of NMR and hydrogen exchange for exploring early stages of protein folding and intrinsic disorder. By coupling NMR-detected H/D exchange with ultrafast quenched-flow mixing we have been able to obtain residue-specific structural insight into the ensemble of states populated during the initial stages of folding of cytochrome c (Fazelinia, H.; Xu, M.; Cheng, H.; Roder, H. J. Am. Chem. Soc. 2014, 136, 733-40). The pH-dependence of amide protection, combined with direct measurement of intrinsic exchange rates in the unfolded protein, showed that amide protons in three α-helical segments in the C-terminal half of cytochrome c were preferentially protected from solvent exchange within 100 microseconds of initiating the folding reaction while the N-terminal α-helix remained unprotected. Thus, sequence-local helix-helix contacts are formed preferentially during early stages of folding whereas long-range (N- to C-terminal) become important only during the later stages of folding (> 3 ms). These findings provide compelling evidence that specific structural events rather than a general hydrophobic collapse of the protein chain dominate the initial stages of folding. I will also present recent progress in our studies on the dynamic properties and functional role of intrinsically disordered regions in NHERF1, a 358-residue protein containing a pair of PDZ domains and a C-terminal motif separated by long flexible linkers. Structural and dynamic NMR, along with other biophysical methods, are providing detailed insight into the conformational equilibria and binding properties of this signaling adaptor.