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Complex between nidogen and laminin fragments reveals a paradigmatic β-propeller interface

Nature volume 424, pages 969–974 (2003)Cite this article

Abstract

Basement membranes are fundamental to tissue organization and physiology in all metazoans. The interaction between laminin and nidogen is crucial to the assembly of basement membranes1,2,3,4. The structure of the interacting domains reveals a six-bladed Tyr-Trp-Thr-Asp (YWTD) β-propeller domain in nidogen bound to laminin epidermal-growth-factor-like (LE) modules III3–5 in laminin (LE3–5). Laminin LE module 4 binds to an amphitheatre-shaped surface on the pseudo-6-fold axis of the β-propeller, and LE module 3 binds over its rim. A Phe residue that shutters the water-filled central aperture of the β-propeller, the rigidity of the amphitheatre, and high shape complementarity enable the construction of an evolutionarily conserved binding surface for LE4 of unprecedentedly high affinity for its small size5. Hypermorphic mutations in the Wnt co-receptor LRP5 (refs 6–9) suggest that a similar YWTD β-propeller interface is used to bind ligands that function in developmental pathways. A related interface, but shifted off-centre from the pseudo-6-fold axis and lacking the shutter over the central aperture, is used in the low-density lipoprotein receptor for an intramolecular interaction that is regulated by pH in receptor recycling10.

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Figure 1: Nidogen and laminin fragment complexes.
Figure 2: The nidogen β-propeller complex with laminin modules LE3–5 and comparison with the LDLR β-propeller.
Figure 3: Sequence alignment.
Figure 4: The nidogen–laminin interaction and comparison with the interaction in the LDLR.

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Acknowledgements

We thank R. Zhang and A. Joachimiak for beamline help, and S. Blacklow and R. Timpl for critically reading the manuscript. This work was supported by an NIH grant.

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Author notes

  1. Junichi Takagi and Yuting Yang: These authors contributed equally to this work

Authors and Affiliations

  1. The Center for Blood Research, Boston, Massachusetts, 02115, USA

    Junichi Takagi & Timothy A. Springer

  2. Dana-Farber Cancer Institute, Boston, Massachusetts, 02115, USA

    Yuting Yang, Jin-huan Liu & Jia-huai Wang

  3. Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Junichi Takagi & Jia-huai Wang

  4. Department of Medicine, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Yuting Yang & Jin-huan Liu

  5. Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Timothy A. Springer

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Correspondence to Jia-huai Wang or Timothy A. Springer.

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Takagi, J., Yang, Y., Liu, Jh. et al. Complex between nidogen and laminin fragments reveals a paradigmatic β-propeller interface. Nature 424, 969–974 (2003). https://doi.org/10.1038/nature01873

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