9X64

Crystal structure of DKK4 CRD1 domain

Summary for 9X64

• Entry DOI: 10.2210/pdb9x64/pdb
• Descriptor: Dickkopf-related protein 4, CHLORIDE ION, NITRATE ION, ... (4 entities in total)
• Functional Keywords: wnt signaling, cystein-rich domain 1, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 15691.28

Authors

Shibata, N. (deposition date: 2025-10-14, release date: 2026-07-15)

Primary citation

Shibata, N.
Crystal structure of human Dickkopf 4 cysteine-rich domain 1 and evaluation of conformational rigidity.
Acta Crystallogr.,Sect.F, 82:245-251, 2026

PubMed Abstract: Dickkopf (DKK) family proteins (DKK1-DKK4), which function as extracellular modulators of Wnt signaling, contain two cysteine-rich domains: CRD1 and CRD2. In DKK1, CRD1 modulates interaction with its receptor low-density lipoprotein receptor-related protein (LRP) 5/6, whereas CRD2 directly binds to LRP5/6. The crystal structure of human DKK4-CRD1 was determined at 1.83 Å resolution. Crystals were obtained from refolded protein expressed as inclusion bodies and belonged to space group P2, with two molecules in the asymmetric unit. Initial molecular-replacement attempts using the solution NMR structure were unsuccessful, whereas an AlphaFold2-predicted model provided a clear solution. The refined structure reveals a compact fold comprising N- and C-subdomains connected by a linker region and stabilized by five conserved disulfide bonds. The crystal structure closely resembles the AlphaFold2 model, but shows larger deviations from the NMR ensemble. ANSURR analysis and hydrogen-bond comparisons indicate that the NMR models underestimate structural rigidity, particularly in β-sheet regions, owing to fewer stabilizing hydrogen bonds. Notably, enhanced conformational variability is observed in the N-subdomain, suggesting a potential role for structural plasticity in ligand recognition.

PubMed: 42328976
DOI: 10.1107/S2053230X26006333

Experimental method

X-RAY DIFFRACTION (1.83 Å)