Biomedical subjects

Declan A Doyle

Publications and source records attributed to Declan A Doyle.

6 recordsLinked to original sources

PubMed2004

Structural themes in ion channels.

The recent crystal structure of the prokaryotic inwardly rectifying potassium channel, KirBac1.1, revealed for the first time the structure of a K+ channel in the closed state plus the location of the activation gate. Comparison of the KirBac1.1 structure with other known ion channels reveals a number of common structural features. These common characteristics include the formation of the ion conduction pathway at the interface between adjacent subunits, non-fixed charges forming part of the ion pathway, electrostatic sinks drawing ions into the channel, helix dipoles, and hydrophobic gates that ultimately prevent ion movement. This review describes in detail common structural themes present in ion channels.

Bacterial Proteins↗

PubMed2004

Potassium channel structures: do they conform?

Potassium channels are signalling elements vital to vertebrate neurotransmission, and cardiac and renal function. Two inherent qualities equip them for their role in the interconversion of chemical and electrical messages: high selectivity for potassium ions and the ability to open (gate) on cue. The crystal structure of KcsA, published in 1998, explained much about potassium selectivity and high ion flux. The enormous diversity of potassium channels (some hundreds of genes in humans) may have hampered similar progress in understanding gating processes. The recent determination of several representative structures has provided us with a valuable reference for discriminating between features that are utilized in gating across the potassium channel genre and features that determine responsiveness to family-specific gating cues.

Ion Channel Gating↗

PubMed2004

Structural changes during ion channel gating.

Ion channels are generally multi-subunit complexes, with the ion conduction pathway formed at the subunit interface. In moving between the closed and open states, three structurally distinct channels, represented by the recently determined structures of a mechanosensitive, ligand-gated and K(+) selective channel, all move transmembrane helices away from the central ion conduction pathway. In all three cases, this results in the displacement of a hydrophobic gate from the ion conduction pathway, freeing ion movement. The channels achieve this by moving the transmembrane helices as rigid bodies using three major types of motion: MscL tilts its helices, the nicotinic ACh receptor rotates its helices, and KirBac1.1 bends its helices. In all cases, the gating motions are likely to take place rapidly. These large and fast movements provide a possible explanation for why the conduction pathways of a wide range of different ion channels are formed at the interface between subunits.

Amino Acid Sequence↗

PubMed2003

Crystal structure of the potassium channel KirBac1.1 in the closed state.

The KirBac1.1 channel belongs to the inward-rectifier family of potassium channels. Here we report the structure of the entire prokaryotic Kir channel assembly, in the closed state, refined to a resolution of 3.65 angstroms. We identify the main activation gate and structural elements involved in gating. On the basis of structural evidence presented here, we suggest that gating involves coupling between the intracellular and membrane domains. This further suggests that initiation of gating by membrane or intracellular signals represents different entry points to a common mechanistic pathway.

Amino Acid Sequence↗

PubMed2003

Increasing the diffraction limit and internal order of a membrane protein crystal by dehydration.

It is notoriously difficult to produce crystals of membrane proteins that diffract to sufficient resolution for structural studies by X-ray crystallography. Crystals of a prokaryotic CLC chloride channel that were initially unacceptable for structural analysis improved in both quality and diffraction limit by a process of dehydration. The loss of water decreased the dimensions of the unit cell axes by up to 25 A, improved the diffraction limit from 8.0 to 4.0 A, and decreased the mosaicity to values of approximately 1 degrees. Dehydration of integral membrane protein crystals should be one of the procedures included in the initial screening for appropriate crystals and as a method of improving the diffraction limits of existing crystals.

Cell Membrane↗

PubMedDate not supplied

Molecular insights into ion channel function (Review).

Water is probably the most important molecule in biology. It solvates molecules, all biochemical reactions occur in it and it is a major driving force in protein folding. Phospholipid membranes separate different water environments, but connections do exist between the different compartments. The integral membrane proteins (IMPs) form these connections. In the case of ions, IMPs form the passageways that regulate ion movement across the membrane. Structural information from three ion distinct channels are examined to see how these channels first select for and then control the movement of their target ions. This review focuses on how these channels select for target ions and control their movement while taking into account and using different properties of water. This includes the use of hydrophobic gates, mimicking the water environment, and controlling ions indirectly by controlling water.

Animals↗