Details

Autor(en) / Beteiligte

• Hakeem, Atiya Y

Titel

The function of aromatic residues in K+ channel gating

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

1998

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• In physiological solutions, Shaker K$\sp+$ channels conduct K$\sp+$ and exclude Na$\sp+$ and other cations. In the absence of internal K$\sp+$ ions, these channels can conduct Na$\sp+$, and in their C-type inactivated state, they conduct Na$\sp+$ but exclude K$\sp+$. The channel must therefore have a selectivity mechanism capable of discriminating between cations. The pore region of the Shaker K$\sp+$ channel contains a number of aromatic residues which are extremely important in the determination of ionic selectivity and the change in selectivity that is C-type inactivation. Mutation of pore domain residues Y445, W434, and W435 to phenylalanine produces a variety of changes in selectivity and rate of C-type inactivation. This data suggests that a hydrogen-bonding interaction between the Y445 and W434 residues is important for normal channel selectivity and rate of C-type inactivation. The W435 residue is also involved in determining selectivity, possibly through direct interactions between its aromatic sidechain and permeating ions. Mutation of either residue W434 or W435 to a hydrophobic or non-aromatic polar residue produces a channel that does not conduct large amounts of K$\sp+$, but instead conducts small amounts of Ca$\sp{2+}$. This implies that the aromaticity of the sidechains of these residues is essential for the normal functioning of the selectivity filter.