Membrane lipids and transporter function

Stieger, Bruno; Steiger, Julia; Locher, Kaspar P.

doi:10.1016/j.bbadis.2021.166079

Cited by 37 publications

(24 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Investigators know how much they put into buffers and all the purification steps, but do not have immediate feedback on what is left around the membrane protein. Additionally, detergents can have side effects, varying from mild loss of activity to complete denaturation in extreme cases [ 1 , 3 , 43 , 44 , 45 ]. Since the effect of detergents is hard to grasp, false impression can originate and lead to misleading data interpretation.…”

Section: Discussionmentioning

confidence: 99%

The Det.Belt Server: A Tool to Visualize and Estimate Amphipathic Solvent Belts around Membrane Proteins

et al. 2021

View full text Add to dashboard Cite

Detergents wrap around membrane proteins to form a belt covering the hydrophobic part of the protein serving for membrane insertion and interaction with lipids. The number of detergent monomers forming this belt is usually unknown to investigators, unless dedicated detergent quantification is undertaken, which for many projects is difficult to setup. Yet, having an approximate knowledge of the amount of detergent forming the belt is extremely useful, to better grasp the protein of interest in interaction with its direct environment rather than picturing the membrane protein “naked”. We created the Det.Belt server to dress up membrane proteins and represent in 3D the bulk made by detergent molecules wrapping in a belt. Many detergents are included in a database, allowing investigators to screen in silico the effect of different detergents around their membrane protein. The input number of detergents is changeable with fast recomputation of the belt for interactive usage. Metrics representing the belt are readily available together with scripts to render quality 3D images for publication. The Det.Belt server is a tool for biochemists to better grasp their sample.

show abstract

Section: Discussionmentioning

confidence: 99%

The Det.Belt Server: A Tool to Visualize and Estimate Amphipathic Solvent Belts around Membrane Proteins

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Some benefits of MLR may not be related to removal of GPL, but instead are likely to be related instead to simple lipid substitution in cellular membranes, such as modulation of ion channels in membranes by MLR supplements to reduce pain and other symptoms. For example, exchanged GPL can modulate the functions of many, if not most cell surface ion channels, transporters, and receptors [323][324][325][326][327][328]. Among numerous possible membrane channels, voltage-gated calcium channels, as well as intracellular calcium channels are particularly important in nerve cells in maintaining trans-membrane potentials and homeostasis [323,327].…”

Section: Mlr: Future Directionsmentioning

confidence: 99%

Fundamentals of Membrane Lipid Replacement: A Natural Medicine Approach to Repairing Cellular Membranes and Reducing Fatigue, Pain, and Other Symptoms While Restoring Function in Chronic Illnesses and Aging

Nicolson

Ferreira

Ash³

et al. 2021

Membranes

View full text Add to dashboard Cite

Membrane Lipid Replacement (MLR) uses natural membrane lipid supplements to safely replace damaged, oxidized lipids in membranes in order to restore membrane function, decrease symptoms and improve health. Oral MLR supplements contain mixtures of cell membrane glycerolphospholipids, fatty acids, and other lipids, and can be used to replace and remove damaged cellular and intracellular membrane lipids. Membrane injury, caused mainly by oxidative damage, occurs in essentially all chronic and acute medical conditions, including cancer and degenerative diseases, and in normal processes, such as aging and development. After ingestion, the protected MLR glycerolphospholipids and other lipids are dispersed, absorbed, and internalized in the small intestines, where they can be partitioned into circulating lipoproteins, globules, liposomes, micelles, membranes, and other carriers and transported in the lymphatics and blood circulation to tissues and cellular sites where they are taken in by cells and partitioned into various cellular membranes. Once inside cells, the glycerolphospholipids and other lipids are transferred to various intracellular membranes by lipid carriers, globules, liposomes, chylomicrons, or by direct membrane–membrane interactions. The entire process appears to be driven by ‘bulk flow’ or mass action principles, where surplus concentrations of replacement lipids can stimulate the natural exchange and removal of damaged membrane lipids while the replacement lipids undergo further enzymatic alterations. Clinical studies have demonstrated the advantages of MLR in restoring membrane and organelle function and reducing fatigue, pain, and other symptoms in chronic illness and aging patients.

show abstract

“…The localizations and activities of transporters are affected by specific lipid environments, such as lipid composition and membrane thickness 44 . Some structural studies of SLC1A transporters reported lipid-binding sites [26][27][28] , and similarly, we observed two flat-shaped densities within each protomer.…”

Section: Putative Functions Of Tm4 Loop and Lipid-binding Sitesmentioning

confidence: 99%

Structural insights into human excitatory amino acid transporter EAAT2

Kato

Kusakizako

Jin

et al. 2021

Preprint

View full text Add to dashboard Cite

Glutamate is a pivotal excitatory neurotransmitter in mammalian brains, but excessive glutamate causes numerous neural disorders. Almost all extracellular glutamate is retrieved by the glial transporter, Excitatory Amino Acid Transporter 2 (EAAT2), belonging to the SLC1A family. However, in some cancers, EAAT2 expression is enhanced and causes resistance to therapies by metabolic disturbance. Despite its crucial roles, the detailed structural information about EAAT2 has not been available. Here, we report cryo-EM structures of human EAAT2 in substrate-free and selective inhibitor WAY213613-bound states. EAAT2 forms a trimer, with each protomer consisting of transport and scaffold domains. Along with a glutamate-binding site, the transport domain possesses a cavity, that could be disrupted during the transport cycle. WAY213613 occupies both the glutamate-binding site and cavity of EAAT2 to interfere with its alternating access, where the sensitivity is defined by the inner environment of the cavity. This is the first characterization of molecular features of EAAT2 and the selective inhibition mechanism, underlying structure-based drug design for EAAT2.

show abstract

Membrane lipids and transporter function

Cited by 37 publications

References 162 publications

The Det.Belt Server: A Tool to Visualize and Estimate Amphipathic Solvent Belts around Membrane Proteins

The Det.Belt Server: A Tool to Visualize and Estimate Amphipathic Solvent Belts around Membrane Proteins

Fundamentals of Membrane Lipid Replacement: A Natural Medicine Approach to Repairing Cellular Membranes and Reducing Fatigue, Pain, and Other Symptoms While Restoring Function in Chronic Illnesses and Aging

Structural insights into human excitatory amino acid transporter EAAT2

Contact Info

Product

Resources

About