Asymmetric contribution of the conserved disulfide loop to subunit oligomerization and assembly of the nicotinic acetylcholine receptor.

The Journal of Biological Chemistry
D X Fu, S M Sine

Abstract

The acetylcholine receptor (AChR) at the motor synapse is a pentamer of homologous subunits with the composition alpha2betagammadelta. Owing to the circular arrangement of subunits that forms a central ion channel, each subunit interface contains contributions from opposite faces of each subunit, designated + and -. Common to all subunits of the AChR and members of its superfamily is a disulfide loop formed between cysteines 128 and 142 of the major extracellular domain. To gain insight into the structural contribution of the disulfide loop and its possible location, we mutated the invariant proline at position 136 to glycine (P136G) and examined subunit assembly. When introduced into any AChR subunit, P136G disrupted assembly by affecting the - face of the subunit, suggesting equivalent positioning of the loop in each subunit and localization to the - face. Also, the contribution of the loop in the overall assembly process differed for each subunit. In the beta and gamma subunits, P136G prevented assembly of higher order heteroligomers, whereas in the alpha and delta subunits, P136G prevented transport of assembled pentamers to the cell surface. The results demonstrate asymmetry in the contribution of the disulfide loop to for...Continue Reading

References

Dec 1, 1990·The Journal of Cell Biology·P Blount, J P Merlie
Jan 1, 1985·Advances in Protein Chemistry·G D RoseJ A Smith
Jan 1, 1983·Cold Spring Harbor Symposia on Quantitative Biology·S NumaS Kikyotani
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·C CzajkowskiA Karlin
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S M Sine

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Citations

Dec 13, 1997·Molecular Neurobiology·J Lindstrom
Jan 14, 2010·The Journal of Biological Chemistry·Walrati LimapichatDennis A Dougherty
Feb 2, 1999·The Journal of General Physiology·S H Keller, P Taylor
Mar 13, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Won Yong LeeSteven M Sine
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·P M EnglandD A Dougherty
Oct 15, 2011·Journal of Physiology, Paris·Cecilia Bouzat
Jan 11, 2011·Journal of Neurochemistry·Victor TsetlinIgor Kasheverov
Jul 19, 2005·Journal of Neuroimmunology·Lorise C GahringScott W Rogers
Sep 23, 2008·Nature Structural & Molecular Biology·Paul S MillerTrevor G Smart
Aug 15, 1997·The Journal of Biological Chemistry·W N Green, C P Wanamaker
May 16, 2002·The Journal of Biological Chemistry·Steven M SineNina Bren
May 21, 2005·The Journal of Physiology·Paul S MillerTrevor G Smart
Jul 20, 2004·The Journal of Biological Chemistry·Joseph SimonEric A Barnard
Aug 10, 2001·The Journal of Biological Chemistry·C M Deane, S C Lummis

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