Dataset Information

Ligand-induced conformational rearrangements regulate the switch between membrane-proximal and distal functions of Rho kinase 2.

ABSTRACT: Rho-associated protein kinase 2 (ROCK2) is a membrane-anchored, long, flexible, multidomain, multifunctional protein. Its functions can be divided into two categories: membrane-proximal and membrane-distal. A recent study concluded that membrane-distal functions require the 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. Binding of RhoA to the coiled-coil domain shifts the equilibrium towards the partially extended state. Enzyme activity measurements suggest that the binding of natural protein substrates 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 study reveals 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.

SUBMITTER: Hajdu I

PROVIDER: S-EPMC7699638 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Ligand-induced conformational rearrangements regulate the switch between membrane-proximal and distal functions of Rho kinase 2.

Hajdú István I Szilágyi András A Végh Barbara M BM Wacha András A Györffy Dániel D Gráczer Éva É Somogyi Márk M Gál Péter P Závodszky Péter P

Communications biology 20201127 1

Rho-associated protein kinase 2 (ROCK2) is a membrane-anchored, long, flexible, multidomain, multifunctional protein. Its functions can be divided into two categories: membrane-proximal and membrane-distal. A recent study concluded that membrane-distal functions require the 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 ...[more]

PMID: 33247217

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Dataset Information

Ligand-induced conformational rearrangements regulate the switch between membrane-proximal and distal functions of Rho kinase 2.

Publications

Ligand-induced conformational rearrangements regulate the switch between membrane-proximal and distal functions of Rho kinase 2.

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