Lysine scanning mutagenesis delineates structural model of the nicotinic receptor ligand binding domain.

Steven M Sine, Hai Long Wang, Nina Bren

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Nicotinic acetylcholine receptors (AChR) and their relatives mediate rapid chemical transmission throughout the nervous system, yet their atomic structures remain elusive. Here we use lysine scanning mutagenesis to determine the orientation of residue side chains toward core hydrophobic or surface hydrophilic environments and use this information to build a structural model of the ligand binding region of the AChR from adult human muscle. The resulting side-chain orientations allow assignment of residue equivalence between AChR subunits and an acetylcholine binding protein solved by x-ray crystallography, providing the foundation for homology modeling. The resulting structural model of the AChR provides a picture of the ACh binding site and predicts novel pairs of residues that stabilize subunit interfaces. The overall results suggest that lysine scanning can provide the basis for structural modeling of other members of the AChR superfamily as well as of other proteins with repeating structures delimiting a hydrophobic core.

Original languageEnglish (US)
Pages (from-to)29210-29223
Number of pages14
JournalJournal of Biological Chemistry
Volume277
Issue number32
StatePublished - Aug 9 2002

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Mutagenesis
Structural Models
Nicotinic Receptors
Cholinergic Receptors
Lysine
Ligands
Scanning
Crystallography
Information use
Neurology
Nervous System
Acetylcholine
Muscle
Carrier Proteins
Binding Sites
X-Rays
X rays
Muscles
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lysine scanning mutagenesis delineates structural model of the nicotinic receptor ligand binding domain. / Sine, Steven M; Wang, Hai Long; Bren, Nina.

In: Journal of Biological Chemistry, Vol. 277, No. 32, 09.08.2002, p. 29210-29223.

Research output: Contribution to journalArticle

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