phosb - Principles of protein phosphorylation Biophysical...

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Unformatted text preview: Principles of protein phosphorylation Biophysical Chemistry 1, Fall 2010 Signalling “cascades” Structural biology of phosphorylation Web assignment: http://pkr.genomics.purdue.edu Kinases and phosphatases eral Examples Signalling overview Cells are way too complex! MAPK/ERK Signaling Pathway Rous sarcoma virus (RSV) Example: Rous sarcoma virus (RSV) Mutations, viruses and cancer Example: Rous sarcoma virus (RSV) Biophysics of signalling Structural Effect of Phosphorylation Phosphorylation is an important regulatory mechanism Can reversible attach/detach a phosphate and therefore switch on / off  the function Signalling by reorientation Reorientation: A conformational switch Disordering: NtrC, a molecular Order/disorder transitions switch upon phosphorylation Alternate Binding: SRC SH2 domain binding Src/SH2 interactions: binding vs release Can we understand Expected conformational effects (predict) the effect of phosphorylation Mutational analysis Experimental data Lubman, O.Y. and Waksman, G. , J Mol Biol 316 (2002) Dissection of the energetic coupling across the Src SH2 domain tyrosyl phosphopeptide interface.  Looking for analogues domains Binding Data Expected conformational effects “Src Homology-2 Domains: Structure, Mechanisms, and Drug Discovery”, Sawyer, Biopolymers, 47, 243-63 (1998) ...
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This note was uploaded on 01/15/2012 for the course CHE 543 taught by Professor Staff during the Fall '10 term at Syracuse.

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