Assoc. Prof. Priv. Doz. Dr. Anna Weinzinger

Gating and conduction regulation of inward rectifier K+ channels

Background / Objective: The primary function of inward rectifier K⁺ channels is to regulate the resting membrane potential of cells, via rectification. This process, which enables the channels to work at negative membrane potentials, is caused by block of outward K⁺ flux by Mg2⁺ and polyamines. The KIR family comprises 15 members, exhibiting high sequence and structure similarity, but remarkable functional diversity, resulting from diverse modulating factors, such as pH, PIP2, G-proteins, ATP and sulphonlyurea receptors. The aim of this project is to unravel the molecular mechanisms of channel regulation by diverse regulatory molecules.

Methods / Networking: By combining molecular dynamics simulations, QM/MM calculations (collaboration with González lab), x-ray crystallography and functional studies (collaboration with Nichols lab, US) and synthesis (collaboration with Maulide lab), this project aims at elucidating the structural mechanisms of rectification.

Expected results: Detailed atomistic understanding of the molecular mechanism of gating of Kir channels.