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Updated: Dec 18, 2025
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Rearing and Double-stranded RNA-mediated Gene Knockdown in the Hide Beetle, Dermestes maculatus
Published on: December 28, 2016
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Structure of the RECK CC domain, an evolutionary anomaly
Tao-Hsin Chang1, Fu-Lien Hsieh1,2, Philip M Smallwood1,2
1Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Summary
The RECK protein's CC-domains are crucial for WNT7 signaling in brain development. Structural analysis of CC4 reveals key residues for GPR124 binding, highlighting the domain's unique evolutionary path.
Area of Science:
- Neuroscience
- Molecular Biology
- Structural Biology
Background:
- The RECK protein contains five N-terminal cysteine-rich domains (CC-domains) vital for WNT7A/WNT7B signaling.
- These signaling pathways are critical for central nervous system (CNS) angiogenesis and blood-brain barrier (BBB) integrity.
Purpose of the Study:
- To elucidate the structure of CC domain 4 (CC4) of the RECK protein.
- To identify critical residues involved in GPR124 binding and WNT7A/WNT7B signaling.
- To investigate the evolutionary uniqueness of CC-domains compared to other ancient protein domains.
Main Methods:
- X-ray crystallography to determine the CC4 structure at 1.65-Å resolution.
- Homology modeling for CC1 structure.
- Sequence and structural homology searches against vertebrate protein databases.
Main Results:
- CC4 adopts a compact four-helix bundle structure stabilized by three disulfide bonds.
- The structure reveals the surface localization of residues essential for GPR124 binding and WNT signaling.
- No homologous domains were found in vertebrates, unlike other ancient domains like EGF or Ig.
Conclusions:
- The determined CC4 structure provides insights into WNT7 signaling mechanisms in CNS development and BBB maintenance.
- The unique evolutionary trajectory of CC-domains suggests a specialized role in vertebrate signaling pathways.
- Further research into CC-domains could reveal novel therapeutic targets for neurological disorders.
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