Issues
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Cover Image
Cover Image
ON THE COVER
The need for hydrophobic adaptation between bilayer-spanning membrane proteins and their host bilayer causes protein conformational changes to alter the packing of the adjacent lipids. This local bilayer deformation incurs an energetic cost, which leads to energetic coupling between the conformational equilibria among different protein states and the bilayer physical properties. Amphiphiles, including drugs and other biologically active compounds, alter lipid bilayer properties when they partition into the bilayer/solution interface, which provides a mechanism by which small molecules may alter membrane protein function without binding to their “target(s).” See page 342. - PDF Icon PDF LinkTable of Contents
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Editorials
Membrane physiologists of all kinds meet at Woods Hole
A special issue of JGP celebrates the 2018 Symposium of the Society of General Physiologists, where diversity and world-class science went hand in hand.
Research News
Rhomboids make do with a weak hydrogen bond
JGP paper explores the strength of the hydrogen bond network at the active site of GlpG.
Commentary
Unlocking the gating mechanism of Kv2.1 using guangxitoxin
Navarro et al discuss new work using the gating-modifier toxin GxTx to investigate the molecular mechanism of Kv2.1 channel gating.
Interrogating the conformational dynamics of BetP transport
Robertson reflects on a new study showing how ensemble-biased metadynamics can be used to interpret BetP protein dynamics data.
Research Articles
The rhomboid protease GlpG has weak interaction energies in its active site hydrogen bond network
Rhomboid proteases are membrane-integrated enzymes that hydrolyze peptide bonds in the transmembrane domains of protein substrates. Gaffney and Hong experimentally determine interaction energies between active site residues to reveal weak coupling, which may explain the slow proteolysis mediated by GlpG.
The tarantula toxin GxTx detains K+ channel gating charges in their resting conformation
Guangxitoxin-1E (GxTx) is a peptide from tarantula venom that binds to Kv2.1 voltage sensors and inhibits channel activity. Tilley et al. investigate the allosteric mechanism of GxTx and show that it stabilizes the resting state of voltage sensors and limits opportunities for the pore to open.
A multiscale model of mechanotransduction by the ankyrin chains of the NOMPC channel
The mechanosensitive channel NOMPC comprises a pore-forming transmembrane domain plus four helical ankyrin repeats that extend into the cytoplasm. Using computational approaches, Argudo et al. show that compression of the ankyrin chains imparts a rotational torque on a putative gating element.
The connexin26 human mutation N14K disrupts cytosolic intersubunit interactions and promotes channel opening
The N14K mutation in the N-terminal domain of connexin26 produces gain-of-function hemichannels. Valdez Capuccino et al. reveal that the mutation disrupts intersubunit interactions between the N terminus and the second transmembrane domain–cytoplasmic loop transition.
Antidepressants are modifiers of lipid bilayer properties
Antidepressants alter the function of their target membrane proteins. They also alter lipid bilayer properties and thereby affect other membrane proteins. Kapoor et al. use gramicidin A channels to probe how antidepressants affect the lipid bilayer, providing a new mechanism for their off-target effects.
Communications
Novel alanine serine cysteine transporter 2 (ASCT2) inhibitors based on sulfonamide and sulfonic acid ester scaffolds
ASCT2 is a transporter that exchanges neutral amino acids such as glutamine across the cell membrane, an essential process for rapidly growing cells, including cancerous ones. Ndaru et al. report the synthesis and characterization of a novel class of inhibitors useful for studying this transporter.
Methods and Approaches
Models to determine the kinetic mechanisms of ion-coupled transporters
Although high-resolution structures are now available for many ion-coupled, or secondary, transporters, the mechanisms by which coupling is achieved remain to be determined. Lolkema and Slotboom derive new mathematical models that can be used to analyze transport data and determine kinetic mechanisms.
Interpretation of spectroscopic data using molecular simulations for the secondary active transporter BetP
Use of spectroscopic techniques to complement structural data and enhance mechanistic understanding of membrane proteins is often complicated by experimental discrepancies. Leone et al. address this challenge by applying an advanced simulation methodology to the interpretation of spectroscopic data for the transporter protein BetP.
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