Biological complexity: ion channel complexity (Introduction)

by David Turell , Friday, October 13, 2017, 23:24 (2598 days ago) @ David Turell

All mammalian cells have this channel to conduct ions properly:

https://phys.org/news/2017-10-d-atomic-trpml1-ion-channel.html

"'Functioning ion channels are needed for the proper movement of electrically charged particles - ions - in and out of cells and organelles to run cellular processes," said Dr. Youxing Jiang, Professor of Physiology and Biophysics, an Investigator in the Howard Hughes Medical Institute (HHMI), and co-corresponding author of the study.

"The TRPML1 channel, which regulates the flow of calcium ions, is found in every mammal. The channel sits in the membrane of organelles inside cells called lysosomes, which contain enzymes that aid in cellular recycling by breaking down large molecules."

The original article abstract:

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature24035.html?foxtrotcallbac...

"Transient receptor potential mucolipin (TRPML1) is a cation channel located within endosomal and lysosomal membranes. Ubiquitously expressed in mammalian cells1, its loss-of-function mutations are the direct cause of type IV mucolipidosis, an autosomal recessive lysosomal storage disease3. Here we present the single-particle electron cryo-microscopy structure of the mouse TRPML1 channel embedded in nanodiscs. Combined with mutagenesis analysis, the TRPML1 structure reveals that phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2) binds to the N terminus of the channel—distal from the pore—and the helix–turn–helix extension between segments S2 and S3 probably couples ligand binding to pore opening. The tightly packed selectivity filter contains multiple ion-binding sites, and the conserved acidic residues form the luminal Ca2+-blocking site that confers luminal pH and Ca2+ modulation on channel conductance. A luminal linker domain forms a fenestrated canopy atop the channel, providing several luminal ion passages to the pore and creating a negative electrostatic trap, with a preference for divalent cations, at the luminal entrance. The structure also reveals two equally distributed S4–S5 linker conformations in the closed channel, suggesting an S4–S5 linker-mediated PtdInsP2 gating mechanism among TRPML channels."

Comment: Be sure to look at the links to see how highly complex this controlling pore has to be. Certainly not by chance. Design required.