Crystal structure of the Ig1 domain of the neural cell adhesion molecule NCAM2 displays domain swapping

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Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO
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Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO

Published on: December 28, 2019

Kim K Rasmussen1, Nikolaj Kulahin, Ole Kristensen

  • 1Protein Laboratory, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.

Journal of Molecular Biology
|August 19, 2008
PubMed

Insights

Neural cell adhesion molecule 2 (NCAM2) forms dimers through beta-strand swapping in its Ig1 domain. This structural finding suggests a novel mechanism for homophilic binding in immunoglobulin superfamily cell adhesion molecules.

Area of Science:

  • Structural biology
  • Molecular and cell biology
  • Neuroscience

Background:

  • Neural cell adhesion molecule 2 (NCAM2) belongs to the immunoglobulin superfamily of cell adhesion molecules (IgCAMs).
  • Understanding the structural basis of NCAM2 function is crucial for elucidating cell adhesion mechanisms.

Purpose of the Study:

  • To determine the crystal structure of the first immunoglobulin (Ig1) domain of NCAM2.
  • To investigate the potential role of domain swapping in NCAM2-mediated interactions.

Main Methods:

  • X-ray crystallography was used to determine the structure of the NCAM2 Ig1 domain at 2.7 A resolution.
  • Gel-filtration chromatography was employed to assess NCAM2 Ig1 dimerization in solution.

Main Results:

  • The crystal structure revealed that two NCAM2 Ig domains interact via beta-strand swapping, where N-terminal beta-strands are interchanged.
  • This beta-strand swapping mechanism, previously observed in cadherins, has not been documented in IgCAMs.
  • Gel-filtration confirmed that NCAM2 Ig1 can form dimers in solution.

Conclusions:

  • The observed beta-strand swapping in the NCAM2 Ig1 domain suggests a potential mechanism for homophilic binding.
  • This finding expands the known structural mechanisms of cell adhesion within the IgCAM superfamily.

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