Structural characterization of the extracellular domain of CASPR2 and insights into its association with the novel ligand Contactin1

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dc.contributor.authorRubio-Marrero, Eva N.
dc.contributor.authorVincelli, Gabriele
dc.contributor.authorJeffries, Cy M.
dc.contributor.authorShaikh, Tanvir R.
dc.contributor.authorPakos, Irene S.
dc.contributor.authorRanaivoson, Fanomezana M.
dc.contributor.authorvon Daake, Sventja
dc.contributor.authorDemeler, Borries
dc.contributor.authorDe Jaco, Antonella
dc.contributor.authorPerkins, Guy
dc.contributor.authorEllisman, Mark H.
dc.contributor.authorTrewhella, Jill
dc.contributor.authorComoletti, Davide
dc.date.accessioned2021-10-13T19:58:58Z
dc.date.available2021-10-13T19:58:58Z
dc.date.issued2015
dc.descriptionOpen access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) appliesen_US
dc.description.abstractContactin-associated protein-like 2 (CNTNAP2) encodes for CASPR2, a multidomain single transmembrane protein belonging to the neurexin superfamily that has been implicated in a broad range of human phenotypes including autism and language impairment. Using a combination of biophysical techniques, including small angle x-ray scattering, single particle electron microscopy, analytical ultracentrifugation, and bio-layer interferometry, we present novel structural and functional data that relate the architecture of the extracellular domain of CASPR2 to a previously unknown ligand, Contactin1 (CNTN1). Structurally, CASPR2 is highly glycosylated and has an overall compact architecture. Functionally, we show that CASPR2 associates with micromolar affinity with CNTN1 but, under the same conditions, it does not interact with any of the other members of the contactin family. Moreover, by using dissociated hippocampal neurons we show that microbeads loaded with CASPR2, but not with a deletion mutant, co-localize with transfected CNTN1, suggesting that CNTN1 is an endogenous ligand for CASPR2. These data provide novel insights into the structure and function of CASPR2, suggesting a complex role of CASPR2 in the nervous system.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationRubio-Marrero, E. N., Vincelli, G., Jeffries, C. M., Shaikh, T. R., Pakos, I. S., Ranaivoson, F. M., von Daake, S., Demeler, B., De Jaco, A., Perkins, G., Ellisman, M. H., Trewhella, J., & Comoletti, D. (2015). Structural characterization of the extracellular domain of CASPR2 and insights into its association with the novel ligand Contactin1. Journal of Biological Chemistry, 291(11), 5788-5802. https://doi.org/10.1074/jbc.M115.705681en_US
dc.identifier.urihttps://hdl.handle.net/10133/6059
dc.language.isoen_USen_US
dc.publisherASBMB Publicationsen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionRutgers Universityen_US
dc.publisher.institutionUniversity of Sydneyen_US
dc.publisher.institutionMasaryk Universityen_US
dc.publisher.institutionUniversity of Texas Health Science Center at San Antonioen_US
dc.publisher.institutionSapienza University of Romeen_US
dc.publisher.institutionUniversity of California San Diegoen_US
dc.publisher.institutionUniversity of Utahen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.urlhttps://doi.org/10.1074/jbc.M115.705681en_US
dc.subjectAnalytical ultracentrifugationen_US
dc.subjectLigand-binding proteinen_US
dc.subjectMolecular cell biologyen_US
dc.subjectProtein structureen_US
dc.subjectCASPR2
dc.subjectContactin1
dc.subject.lcshLigand binding (Biochemistry)
dc.subject.lcshSmall-angle x-ray scattering
dc.subject.lcshUltracentrifugation
dc.titleStructural characterization of the extracellular domain of CASPR2 and insights into its association with the novel ligand Contactin1en_US
dc.typeArticleen_US
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