Összes szerző

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Végh Barbara

az alábbi absztraktok szerzői között szerepel:

Závodszky Péter
Ligand-induced conformational rearrangements regulate the switch between functions of ROCK2

Aug 27 - kedd

17:00 – 19:00

I. Poszterszekció

P17

Ligand-induced conformational rearrangements regulate the switch between functions of ROCK2 

István Hajdú¹, András Szilágyi¹, Barbara Végh¹, András Wacha² Éva Gráczer¹, Dániel Györffy¹, Márk Somogyi¹, Péter Závodszky¹

¹Institute of Enzymology, RCNS, HAS, Budapest,

²Institute of Materials and Environmental Chemistry. RCNS, HAS, Budapest

Rho-associated protein kinase 2 (ROCK2) is a membrane-anchored, long, flexible, multidomain, multifunctional protein. Its functions can be placed into two categories: membrane-proximal and membrane-distal ones. A recent study concluded that membrane–distal functions, e.g. regulatory myosin light chain (RMLC) phosphorylation requires a fully extended conformation, and this conclusion was supported by electron microscopy. The present solution small angle X-ray scattering (SAXS) study revealed that ROCK2 population is a dynamic mixture of folded and partially extended conformers. We have shown that the predicted, auto-inhibited, folded conformation of ROCK2 exists in solution, and is stabilized by weak non-covalent interactions between the N- and C-termini. Binding of RhoA to the coiled-coil domain shifts the equilibrium towards the partially extended state. The binding of natural protein substrates (e.g. LIMK1) to the kinase domain breaks up the interaction between the N-terminal kinase and C-terminal regulatory domains, but smaller substrate analogues do not. The present studies reflect the dynamic behaviour of this long, dimeric molecule in solution, and our structural model provides a mechanistic explanation for a set of membrane-proximal functions, while allowing for the existence of an extended conformation in the case of membrane-distal functions.