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dc.contributor.author Rubio-Marrero, Eva N.
dc.contributor.author Vincelli, Gabriele
dc.contributor.author Jeffries, Cy M.
dc.contributor.author Shaikh, Tanvir R.
dc.contributor.author Pakos, Irene S.
dc.contributor.author Ranaivoson, Fanomezana M.
dc.contributor.author von Daake, Sventja
dc.contributor.author Demeler, Borries
dc.contributor.author De Jaco, Antonella
dc.contributor.author Perkins, Guy
dc.contributor.author Ellisman, Mark H.
dc.contributor.author Trewhella, Jill
dc.contributor.author Comoletti, Davide
dc.date.accessioned 2021-10-13T19:58:58Z
dc.date.available 2021-10-13T19:58:58Z
dc.date.issued 2015
dc.identifier.citation Rubio-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.M115.705681 en_US
dc.identifier.uri https://hdl.handle.net/10133/6059
dc.description Open access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) applies en_US
dc.description.abstract Contactin-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.language.iso en_US en_US
dc.publisher ASBMB Publications en_US
dc.subject Analytical ultracentrifugation en_US
dc.subject Ligand-binding protein en_US
dc.subject Molecular cell biology en_US
dc.subject Protein structure en_US
dc.subject CASPR2
dc.subject Contactin1
dc.subject.lcsh Ligand binding (Biochemistry)
dc.subject.lcsh Small-angle x-ray scattering
dc.subject.lcsh Ultracentrifugation
dc.title Structural characterization of the extracellular domain of CASPR2 and insights into its association with the novel ligand Contactin1 en_US
dc.type Article en_US
dc.publisher.faculty Arts and Science en_US
dc.publisher.department Department of Chemistry and Biochemistry en_US
dc.description.peer-review Yes en_US
dc.publisher.institution Rutgers University en_US
dc.publisher.institution University of Sydney en_US
dc.publisher.institution Masaryk University en_US
dc.publisher.institution University of Texas Health Science Center at San Antonio en_US
dc.publisher.institution Sapienza University of Rome en_US
dc.publisher.institution University of California San Diego en_US
dc.publisher.institution University of Utah en_US
dc.publisher.institution University of Lethbridge en_US
dc.publisher.url https://doi.org/10.1074/jbc.M115.705681 en_US


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