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Structure and interactions of NCAM modules 1 and 2, basic elements in neural cell adhesion

Nature Structural Biology volume 6, pages 486–493 (1999)Cite this article

Abstract

The structure in solution of the second Ig-module fragment of residues 117–208 of NCAM has been determined. Like the first Ig-module of residues 20–116, it belongs to the I set of the immunogloblin superfamily. Module 1 and module 2 interact weakly, and the binding sites of this interaction have been identified. The two–module fragment NCAM(20–208) is a stable dimer. Removal of the charged residues in these sites in NCAM(20–208) abolishes the dimerization. Modeling the dimer of NCAM(20–208) to fit the interactions of these charges produces one coherent binding site for the formation of two antiparallel strands of the first two NCAM modules. This mode of binding could be a major element in trans–cellular interactions in neural cell adhesion.

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Figure 1: The structure of module 2 of NCAM as determined by NMR spectroscopy.
Figure 2: Identification of residues in the binding sites in module 1 and 2 using chemical shift changes for 15N and 1H resonance lines of the H-N groups.
Figure 3: The electrostatic surfaces of the two modules and their binding sites.
Figure 4: Upfield and downfield regions of 750 MHz 1H NMR spectra of:
Figure 5: Titration curve from the changes of the chemical shift of the 15N resonance line of Glu 198 in a titration experiment where unlabeled module 1 was added to 15N-labeled module 2.
Figure 6: Model building of the dimer of NCAM(20–208) in a MOLMOL ribbon presentation.
Figure 7: The dimer of NCAM(20–208).

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Acknowledgements

The group at the Protein Laboratory was supported by the Danish Biotechnology Programme, The Lundbeck Foundation, the Danish Cancer Society, and The EU programme on Biotechnology. The group at the Carlsberg Laboratory was supported by The Danish Biotechnology Programme. This is a contribution from the Danish Instrument Center for NMR spectroscopy of Biological Macromolecules.

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Author notes

  1. Peter Holme Jensen

    Present address: Institute of Molecular Biology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353, Copenhagen, Denmark

  2. Peter Holme Jensen and Vladislav Soroka: These two authors contributed equally to the work presented here.

Authors and Affiliations

  1. Department of Chemistry, Carlsberg Laboratory, Gamle Carlsberg Vej 10, Valby, DK-2500, Denmark

    Peter Holme Jensen, Vladislav Soroka, Niels Kirk Thomsen & Flemming M. Poulsen

  2. Protein Laboratory, Institute of Molecular Pathology, Panum Institute, University of Copenhagen, Copenhagen N., DK-2200, Denmark

    Vladislav Soroka, Igor Ralets, Vladimir Berezin & Elisabeth Bock

  3. Institute of Molecular Biology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353, Copenhagen, Denmark

    Flemming M. Poulsen

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Correspondence to Flemming M. Poulsen.

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Jensen, P., Soroka, V., Thomsen, N. et al. Structure and interactions of NCAM modules 1 and 2, basic elements in neural cell adhesion. Nat Struct Mol Biol 6, 486–493 (1999). https://doi.org/10.1038/8292

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