scholarly journals Molecular structure and function of myelin protein P0 in membrane stacking

2018 ◽  
Author(s):  
Arne Raasakka ◽  
Salla Ruskamo ◽  
Julia Kowal ◽  
Huijong Han ◽  
Anne Baumann ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Transmembrane Helix ◽  
Myelin Protein ◽  
Myelin Membrane ◽  
Double Structure ◽  
Physiological Importance ◽  
Cytoplasmic Extension ◽  
Extracellular Compartment ◽  
Pns Myelin ◽  
And Function

AbstractCompact myelin forms the basis of nerve insulation essential for higher vertebrates. Dozens of myelin membrane bilayers undergo tight stacking, and in the peripheral nervous system, this is partially enabled by myelin protein zero (P0). Consisting of an immunoglobulin (Ig)-like extracellular domain, a single transmembrane helix, and a cytoplasmic extension (P0ct), P0 harbours an important task in ensuring the integrity of compact myelin in the extracellular compartment, referred to as the intraperiod line. Several disease mutations resulting in peripheral neuropathies have been identified for P0, reflecting its physiological importance, but the arrangement of P0 within the myelin ultrastructure remains obscure. We performed a biophysical characterization of recombinant P0ct. P0ct contributes to the binding affinity between apposed cytoplasmic myelin membrane leaflets, which not only results in fluidity changes of the bilayers themselves, but also potentially involves the rearrangement of the Ig-like domains in a manner that stabilizes the intraperiod line. Transmission electron cryomicroscopy of native full-length P0 showed that P0 stacks lipid membranes by forming antiparallel dimers between the extracellular Ig-like domains. The zipper-like arrangement of the P0 extracellular domains between two membranes explains the double structure of the myelin intraperiod line. Our results contribute to the understanding of PNS myelin, the role of P0 therein, and the underlying molecular foundation of compact myelin stability in health and disease.

scholarly journals The role of prolines and glycine in the transmembrane domain of LAT

2020 ◽  
Author(s):  
Daniela Glatzová ◽  
Harsha Mavila ◽  
Maria Chiara Saija ◽  
Tomáš Chum ◽  
Lukasz Cwiklik ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasma Membrane ◽  
Transmembrane Domain ◽  
Transmembrane Helix ◽  
Helical Structure ◽  
Surface Expression ◽  
Transmembrane Segment ◽  
Proline Residue ◽  
And Function ◽  
The Impact

ABSTRACTLAT is a critical regulator of T cell development and function. It organises signalling events at the plasma membrane. However, the mechanism, which controls LAT localisation at the plasma membrane is not fully understood. Here, we studied the impact of helix-breaking amino acids, two prolines and one glycine, in the transmembrane segment on localisation and function of LAT. Using in silico analysis, confocal and superresolution imaging and flow cytometry we demonstrate that central proline residue destabilises transmembrane helix by inducing a kink. The helical structure and dynamics is further regulated by glycine and another proline residue in the luminal part of LAT transmembrane domain. Replacement of these residues with aliphatic amino acids reduces LAT dependence on palmitoylation for sorting to the plasma membrane. However, surface expression of these mutants is not sufficient to recover function of non-palmitoylated LAT in stimulated T cells. These data indicate that geometry and dynamics of LAT transmembrane segment regulate its localisation and function in immune cells.

scholarly journals Influence of Transmembrane Helix Mutations on Cytochrome P450-Membrane Interactions and Function

2019 ◽  
Vol 116 (3) ◽  
pp. 419-432 ◽  
Author(s):  
Ghulam Mustafa ◽  
Prajwal P. Nandekar ◽  
Tyler J. Camp ◽  
Neil J. Bruce ◽  
Michael C. Gregory ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Transmembrane Helix ◽  
Membrane Interactions ◽  
And Function

scholarly journals Transmembrane signaling and cytoplasmic signal conversion by dimeric transmembrane helix 2 and a linker domain of the DcuS sensor kinase

2020 ◽  
pp. jbc.RA120.015999
Author(s):  
Marius Stopp ◽  
Philipp Aloysius Steinmetz ◽  
Christopher Schubert ◽  
Christian Griesinger ◽  
Dirk Schneider ◽  
...  
Keyword(s):  
Signal Transmission ◽  
Transmembrane Helix ◽  
Helical Structure ◽  
Kinase Domain ◽  
Sensor Kinase ◽  
Transmembrane Signaling ◽  
Activated State ◽  
Sensor Kinases ◽  
And Function ◽  
Cytoplasmic Side

Transmembrane signaling is a key process of membrane bound sensor kinases. The C4-dicarboxylate (fumarate) responsive sensor kinase DcuS of Escherichia coli is anchored by transmembrane helices TM1 and TM2 in the membrane. Signal transmission across the membrane relies on the piston-type movement of the periplasmic part of TM2. To define the role of TM2 in transmembrane signaling, we use oxidative Cys cross-linking to demonstrate that TM2 extends over the full distance of the membrane and forms a stable transmembrane homodimer in both the inactive and fumarate-activated state of DcuS. A S186xxxGxxxG194 motif is required for the stability and function of the TM2 homodimer. The TM2 helix further extends on the periplasmic side into the α6-helix of the sensory PASP domain, and on the cytoplasmic side into the α1-helix of PASC. PASC has to transmit the signal to the C-terminal kinase domain. A helical linker on the cytoplasmic side connecting TM2 with PASC contains a LxxxLxxxL sequence. The dimeric state of the linker was relieved during fumarate activation of DcuS, indicating structural rearrangements in the linker. Thus, DcuS contains a long α-helical structure reaching from the sensory PASP (α6) domain across the membrane to α1(PASC). Taken together, the results suggest piston-type transmembrane signaling by the TM2-homodimer from PASP across the full TM region, whereas the fumarate-destabilized linker dimer converts the signal on the cytoplasmic side for PASC and kinase regulation.

scholarly journals Role of Cysteine Residues in Structural Stability and Function of a Transmembrane Helix Bundle

2001 ◽  
Vol 276 (42) ◽  
pp. 38814-38819 ◽  
Author(s):  
Christine B. Karim ◽  
M. Germana Paterlini ◽  
Laxma G. Reddy ◽  
Gregory W. Hunter ◽  
George Barany ◽  
...  
Keyword(s):  
Structural Stability ◽  
Transmembrane Helix ◽  
Cysteine Residues ◽  
Helix Bundle ◽  
And Function

scholarly journals Analysis of Trafficking, Stability and Function of Human Connexin 26 Gap Junction Channels with Deafness-Causing Mutations in the Fourth Transmembrane Helix

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e70916 ◽  
Author(s):  
Cinzia Ambrosi ◽  
Amy E. Walker ◽  
Adam D. DePriest ◽  
Angela C. Cone ◽  
Connie Lu ◽  
...  
Keyword(s):  
Gap Junction ◽  
Transmembrane Helix ◽  
Connexin 26 ◽  
Gap Junction Channels ◽  
And Function

The effects of H+ upon the gills of freshwater fish

1983 ◽  
Vol 61 (4) ◽  
pp. 691-703 ◽  
Author(s):  
D. G. McDonald
Keyword(s):  
Freshwater Fish ◽  
Calcium Concentration ◽  
Low Ph ◽  
Mucous Secretion ◽  
Physiological Importance ◽  
Gill Structure ◽  
Net Flux ◽  
And Function ◽  
External Calcium ◽  
Gill Function

The structure and function of the gills of freshwater fish are briefly summarized and the responses to low pH are reviewed, with particular reference to the salmonid fishes. Major influences are seen upon ion and acid–base regulatory mechanisms at the gills and upon mucous secretion and gill structure. Ionic imbalances which can be responsible for death at low pH are caused by disturbances to both the active transport and the diffusional losses of Na+ and Cl−. The disturbances, while not identical for the two ions, are similar to the extent that the undirectional fluxes of both are dependent upon the severity and duration of the acid exposure and upon the external calcium concentration. Calcium also has an important influence on the net flux of H+ across the gills. A model is proposed for the interaction of Ca2+ and H+ on gill function. The physiological importance of mucous secretion at low pH is discussed and the issue of whether acid-intolerant species can be successfully adapted for life at low pH is examined.

scholarly journals Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer

2014 ◽  
Vol 111 (10) ◽  
pp. 3865-3870 ◽  
Author(s):  
Brian C. Monk ◽  
Thomas M. Tomasiak ◽  
Mikhail V. Keniya ◽  
Franziska U. Huschmann ◽  
Joel D. A. Tyndall ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Catalytic Domain ◽  
Transmembrane Helix ◽  
Protein Structures ◽  
Antifungal Drugs ◽  
Integral Membrane Proteins ◽  
Ergosterol Biosynthesis ◽  
Amphipathic Helix ◽  
Membrane Spanning ◽  
And Function

Bitopic integral membrane proteins with a single transmembrane helix play diverse roles in catalysis, cell signaling, and morphogenesis. Complete monospanning protein structures are needed to show how interaction between the transmembrane helix and catalytic domain might influence association with the membrane and function. We report crystal structures of full-length Saccharomyces cerevisiae lanosterol 14α-demethylase, a membrane monospanning cytochrome P450 of the CYP51 family that catalyzes the first postcyclization step in ergosterol biosynthesis and is inhibited by triazole drugs. The structures reveal a well-ordered N-terminal amphipathic helix preceding a putative transmembrane helix that would constrain the catalytic domain orientation to lie partly in the lipid bilayer. The structures locate the substrate lanosterol, identify putative substrate and product channels, and reveal constrained interactions with triazole antifungal drugs that are important for drug design and understanding drug resistance.

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