Acetylcholine receptor protein structure

1978 ◽  
Vol 36 (2) ◽  
pp. 180-181
Author(s):  
A. Brisson
Keyword(s):  
Acetylcholine Receptor ◽  
Conformational Changes ◽  
Binding Sites ◽  
Particle Surface ◽  
Cholinergic Receptor ◽  
Transmission Mechanism ◽  
Receptor Protein ◽  
Subunit Structure ◽  
Structural Relationships ◽  
Membrane Bound

The acetylcholine receptor protein plays a leading part in the synaptic transmission mechanism. The binding of the neurotransmitter, acetylcholine, to the protein triggers conformational changes, allowing the translocation of ions through the membrane. The structural relationships between the binding sites of the cholinergic ligands and the translocating part of the protein are still unknown, as the subunit composition is. A better knowledge of the structure of the acetylcholine receptor protein is the aim of the present study.Negatively stained preparations of purified cholinergic receptor protein and of membrane fragments rich in acetylcholine receptor protein are characterized by the presence of particles having a diameter of 8-9 mm, and exhibiting a doughnut like structure, with a central pit filled with stain. The variability in the stain distribution on the particle surface did'nt allow to determine the subunit structure of the protein. In the case of crystalline biological specimens, methods of averaging have allowed to overcome this problem; then, we have tried to crystallize the membrane-bound cholinergic receptor protein.

A simple quantitative assay of 125I-labeled α-bungarotoxin binding to soluble and membrane-bound acetylcholine receptor protein

1977 ◽  
Vol 80 (2) ◽  
pp. 531-539 ◽  
Author(s):  
Ronald A. Kohanski ◽  
John P. Andrews ◽  
Pierre Wins ◽  
Mohyee E. Eldefrawi ◽  
George P. Hess
Keyword(s):  
Acetylcholine Receptor ◽  
Quantitative Assay ◽  
Receptor Protein ◽  
Membrane Bound

scholarly journals Phosphatidic acid inhibits SNARE priming by inducing conformational changes in Sec18 protomers

2018 ◽  
Author(s):  
Matthew L. Starr ◽  
Robert P. Sparks ◽  
Logan R. Hurst ◽  
Zhiyu Zhao ◽  
Andres Arango ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Phosphatidic Acid ◽  
Conformational Changes ◽  
Binding Sites ◽  
Membrane Curvature ◽  
Snare Proteins ◽  
Dependent Manner ◽  
Protein Architecture ◽  
Membrane Bound ◽  
Hexameric Form

SUMMARYEukaryotic homeostasis relies on membrane fusion catalyzed by SNARE proteins. Inactive SNARE bundles are re-activated by Sec18/NSF driven disassembly to enable a new round of fusion. We previously found that phosphatidic acid (PA) binds Sec18 to sequester it from SNAREs. Dephosphorylation of PA dissociates Sec18 from the membrane allowing it to engage SNARE complexes. We now report that PA induces conformational changes in Sec18 protomers, while hexameric Sec18 cannot bind PA membranes. The association of Sec18 with PA was shown to be sensitive to membrane curvature, suggesting that regulation could vary on different organelles in a curvature dependent manner. Molecular dynamics showed that PA binding sites exist on the D1 and D2 domains of Sec18 and that residues needed for binding were masked in the hexameric form of the protein. Together these data indicate that PA regulates Sec18 function through altering protein architecture and stabilizing membrane-bound protomers.

scholarly journals Metastasis of cholangiocarcinoma is promoted by extended high-mannose glycans

2020 ◽  
Vol 117 (14) ◽  
pp. 7633-7644 ◽  
Author(s):  
Diane Dayoung Park ◽  
Chatchai Phoomak ◽  
Gege Xu ◽  
Laura P. Olney ◽  
Khiem A. Tran ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Noncovalent Interaction ◽  
Therapeutic Interventions ◽  
Receptor Protein ◽  
Membrane Glycoproteins ◽  
Promising Target ◽  
Cell Membrane Proteins ◽  
Membrane Bound ◽  
High Mannose ◽  
External Stimuli

Membrane-bound oligosaccharides form the interfacial boundary between the cell and its environment, mediating processes such as adhesion and signaling. These structures can undergo dynamic changes in composition and expression based on cell type, external stimuli, and genetic factors. Glycosylation, therefore, is a promising target of therapeutic interventions for presently incurable forms of advanced cancer. Here, we show that cholangiocarcinoma metastasis is characterized by down-regulation of the Golgi α-mannosidase I coding geneMAN1A1, leading to elevation of extended high-mannose glycans with terminating α-1,2-mannose residues. Subsequent reshaping of the glycome by inhibiting α-mannosidase I resulted in significantly higher migratory and invasive capabilities while masking cell surface mannosylation suppressed metastasis-related phenotypes. Exclusive elucidation of differentially expressed membrane glycoproteins and molecular modeling suggested that extended high-mannose glycosylation at the helical domain of transferrin receptor protein 1 promotes conformational changes that improve noncovalent interaction energies and lead to enhancement of cell migration in metastatic cholangiocarcinoma. The results provide support that α-1,2-mannosylatedN-glycans present on cancer cell membrane proteins may serve as therapeutic targets for preventing metastasis.

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