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Published on: December 10, 2015
Complex between nidogen and laminin fragments reveals a paradigmatic beta-propeller interface
Junichi Takagi1, Yuting Yang, Jin-Huan Liu
1The Center for Blood Research, Boston, Massachusetts 02115, USA.
Nature
|August 22, 2003
Summary
The interaction between laminin and nidogen is crucial for basement membrane assembly. Researchers elucidated the structure of this interaction, revealing a high-affinity binding surface essential for tissue organization.
Area of Science:
- Biochemistry
- Cell Biology
- Structural Biology
Background:
- Basement membranes are essential for tissue organization and physiological functions in metazoans.
- The laminin-nidogen interaction is critical for basement membrane assembly.
Purpose of the Study:
- To determine the structural basis of the laminin-nidogen interaction.
- To understand how this interaction contributes to basement membrane formation and stability.
Main Methods:
- X-ray crystallography to determine the structure of the interacting domains.
- Biochemical assays to characterize binding affinity and specificity.
Main Results:
- The structure reveals nidogen's Tyr-Trp-Thr-Asp (YWTD) beta-propeller domain binding to laminin epidermal-growth-factor-like (LE) modules III3-5.
- Laminin LE module 4 binds to a rigid, amphitheatre-shaped surface on the beta-propeller, while LE module 3 binds to its rim.
- A phenylalanine residue shutters the beta-propeller's central aperture, contributing to a high-affinity binding surface for LE4.
Conclusions:
- The high-affinity interaction between laminin and nidogen is mediated by specific structural features, including shape complementarity and a rigid binding interface.
- This interaction is evolutionarily conserved and fundamental to basement membrane assembly and tissue integrity.
- Similar beta-propeller interfaces are implicated in developmental pathways (e.g., Wnt signaling via LRP5) and receptor recycling (low-density lipoprotein receptor).
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