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Cryo-electron tomography of homophilic adhesion mediated by the neural cell adhesion molecule L1

He, Yongning and Jensen, Grant J. and Bjorkman, Pamela J. (2009) Cryo-electron tomography of homophilic adhesion mediated by the neural cell adhesion molecule L1. Structure, 17 (3). pp. 460-471. ISSN 0969-2126. PMCID PMC2744468. http://resolver.caltech.edu/CaltechAUTHORS:20090410-112112630

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[img] Video (QuickTime) (Movie S4. Six Pairs of Interacting Horseshoes (Modeled using the Dscam/axonin-1 Model Described in Experimental Procedures) Placed into Densities from an Interface Formed by Ig1-6 (CC)-Coupled Liposomes (Figure4D) (MOV 9532 kb)) - Supplemental Material
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Abstract

The neural cell adhesion molecule L1 participates in homophilic interactions important for axon guidance and neuronal development. The structural details of homophilic adhesion mediated by L1 and other immunoglobulin superfamily members containing an N-terminal horseshoe arrangement of four immunoglobulin-like domains are unknown. Here we used cryo-electron tomography to study liposomes to which intact or truncated forms of the L1 ectodomain were attached. Tomographic reconstructions revealed an adhesion interface with a regular and repeating pattern consistent with interactions between paired horseshoes contributed by L1 proteins from neighboring liposomes. The characteristics of the pattern changed when N-linked carbohydrates were altered by removing sialic acids or converting from complex to high mannose or oligomannose glycans, suggesting a regulatory role for carbohydrates in L1-mediated homophilic adhesion. Using the results from tomograms and crystal structures of L1-related molecules, we present a structural model for L1-mediated homophilic adhesion that depends on protein-protein, protein-carbohydrate, and carbohydrate-carbohydrate interactions.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.str.2009.01.009DOIArticle
http://www.cell.com/structure/retrieve/pii/S0969212609000732PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744468/PubMed CentralArticle
ORCID:
AuthorORCID
Jensen, Grant J.0000-0003-1556-4864
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2009 Elsevier Ltd. Received 6 November 2008; revised 5 January 2009; accepted 10 January 2009. Published: March 10, 2009. Available online 10 March 2009. We thank Jost Vielmetter, Inderjit Nangiana, Chris Foglesong and the Caltech Protein Expression Center for expression of proteins, William Tivol and Prabha Dias for help with microscopy, and members of the Bjorkman and Jensen laboratories for helpful suggestions. Mass spectroscopic analysis and N-terminal sequencing performed by the Protein/Peptide Microanalytical Laboratory was supported by The Beckman Institute at Caltech. This work was supported by a postdoctoral fellowship from the Cancer Research Institute (Y.H.), the Howard Hughes Medical Institute (P.J.B.), and gifts to Caltech to support electron microscopy from the Gordon and Betty Moore Foundation and the Agouron Institute.
Funders:
Funding AgencyGrant Number
Cancer Research InstituteUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
Agouron InstituteUNSPECIFIED
Issue or Number:3
PubMed Central ID:PMC2744468
Record Number:CaltechAUTHORS:20090410-112112630
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20090410-112112630
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13927
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 Aug 2009 22:11
Last Modified:24 Mar 2017 22:54

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