Interaction of the collagen-like tail of asymmetric acetylcholinesterase with heparin depends on triple-helical conformation, sequence and stability

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dc.contributor.authorDeprez, P
dc.contributor.authorDoss-Pepe, E
dc.contributor.authorBrodsky, B
dc.contributor.authorInestrosa, NC
dc.date.accessioned2025-01-21T01:31:13Z
dc.date.available2025-01-21T01:31:13Z
dc.date.issued2000
dc.description.abstractThe collagen-like tail of asymmetric acetylcholinesterase (AChE) contains two heparin-binding domains (HBDs) that interact with heparan sulphate proteoglycans, determining the anchoring of the enzyme at the basal lamina and its specific Localization at the neuromuscular junction. Both HBDs are characterized by a cluster of basic residues containing a core with the BBXB consensus sequence (where B represents a basic residue and X a non-basic residue). To study the interaction of such HBDs with heparin we have used synthetic peptides to model the N-terminal and C-terminal sites. CD spectroscopy showed that all peptides are triple-helical at low temperatures, and undergo trimer-to-monomer transitions. Displacement assays of asymmetric AChE bound to heparin were performed using the peptides in both monomeric and triple-helical states. In the monomeric con- formation, all the peptides were able to displace low levels of AChE depending on the basic charge content. In the triplehelical conformation, peptides containing the consensus sequence showed a large increase in the ability to displace bound AChE. Results suggest that the specific binding of the collagen-like-tail peptides to heparin depends both on the presence of the core sequence and on the triple-helical conformation. Moreover, BBXB-containing peptides that are less stable are more effective in displacing AChE, suggesting that the interaction region needs a significant amount of structural flexibility to better accommodate the ligand.
dc.fuente.origenWOS
dc.identifier.issn0264-6021
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/97013
dc.identifier.wosidWOS:000089067100035
dc.language.isoen
dc.pagina.final290
dc.pagina.inicio283
dc.revistaBiochemical journal
dc.rightsacceso restringido
dc.subjectcholinergic
dc.subjectColQ
dc.subjectproteoglycan
dc.subjecttriple-helical peptide
dc.titleInteraction of the collagen-like tail of asymmetric acetylcholinesterase with heparin depends on triple-helical conformation, sequence and stability
dc.typeartículo
dc.volumen350
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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