Ion channel is a family of membrane proteins which mediates the ionic flux between outside and inside cells. The ion selectivity of ion channels is important because each ion plays a different role; sodium depolarize the membrane potential, potassium repolarize the membrane potential, and calcium depolarize the membrane potential and act as an intracellular second messenger. The key of the ion selectivity is the “selectivity filter”. The selectivity filter is in the narrow part of the pore and would confine the ionic permeation through the pore. In the selectivity filter, potassium selective channel contains TVGYG sequence, sodium or calcium selective channel contains anionic residue (D or E) on the fourth position, and non-selective channel shares both features. The protein described here is NaK channel, a ''B. cereus' non-selective cation channel, whose selectivity filter is TVGDG. The structural determinant of potassium ion selectivity in the selectivity filter has revealed by Rod MaCkinon’s group(Rod MaCkinon won the Nobel prize in Chemistry in 2003 for this work). However, the other cation selectivity has not yet been well-characterized. Therefore, this NaK channel structure is the first glimpse of the role of fourth anionic residue in the selectivity filter.
NaK channel shares common features with KcsA, potassium channel in Streptomyces lividans. NaK channel is homotetramer, and each subunit contains two transmembrane helices, M1 and M2, a interfacial amphiphilic helix, M0, a pore helix, P and selectivity filter (fig1). The selectivity filters of KcsA(1BL8) and NaK channel are compared in fig2. In KcsA selectivity filter, the carbonyl oxygen atoms of TVGYG point toward the center of the pore from four subunits. In NaK channel, on the contrary, only oxygen atoms of TV form ionic binding sites. The rest GDG residues point toward the extracellular region and form divalent ion binding site. The type of selectivity filter is seen in the cyclic nucleotide gated(CNG) channel of higher organisms, and would contribute to the broad ion selectivity of the channel.
fig1. Overall structure of NaK channel(Only two subunits are shown). Each subunit is colored red and blue.
fig2. Selectivity filters of KcsA(left) and NaK(right). Oxygen atoms extruded to the pore center, divalent cation binding oxygen atoms in NaK, and aspartate residue of NaK selectivity filter are colored as yellow, green, and purple.
Protein Data Bank (PDB)
Shi, N. Ye, S. Alam, A. Chen, L. Jiang, Y.; "Atomic structure of a Na+- and K+-conducting channel."; Nature; (2006) 440:570-574 PubMed:16467789.
author: Daisuke Ino