Molecular recognition – Viral proteins that fold upon binding

Molecular recognition - Viral proteins that fold upon binding

A key feature of the complex relationship between structural dynamics and biological function in intrinsically unfolded proteins is the observed capacity of some members of this family to undergo a disorder-to-order transition on interaction with a physiological partner. In these systems molecular recognition is often accompanied by local folding into a characteristic three-dimensional conformation.

In close collaboration with Professor Ruigrok and Professor Marc Jamin, at the UVHCI, we have developed techniques to characterise the level of intrinsic structure in the pre-recognition state of viral proteins that fold upon binding and are involved in transcription and replication. We have applied this approach to the nucleoprotein from Sendai virus, that interacts with partially folded phosphoprotein during transcription and replication. We find that three different helical elements are populated in solution, each of them being preceded by a known n-capping motif that appears to stabilize these selected helices prior to interaction.

We are currently studying the combination of disorder/order transitions, encounter complexes and transient binding modes that constitute the dynamics of this and related systems.

Quantitative Conformational Analysis of Partially Folded Proteins from Residual Dipolar Couplings : Application to the Molecular Recognition Element of Sendai Virus Nucleoprotein. Malene Ringkjobing Jensen, Klaartje Houben, Ewen Lescop, Laurence Blanchard, Rob W.H. Ruigrok and Martin Blackledge. J.Am.Chem.Soc.130, 8055-8061 (2008).

Intrinsic dynamics of the partly unstructured PX domain from the Sendai virus RNA polymerase co-factor. P. K. Houben, L. Blanchard, M. Blackledge and D. Marion. Biophysical Journal93, 2830-2844(2007).