6WBJ

High resolution crystal structure of mRECK(CC4) in fusion with engineered MBP

Summary for 6WBJ

• Entry DOI: 10.2210/pdb6wbj/pdb
• Related: 6WBH
• Related PRD ID: PRD_900001
• Descriptor: Maltodextrin-binding protein,Reversion-inducing cysteine-rich protein with Kazal motifs fusion, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, SULFATE ION, ... (6 entities in total)
• Functional Keywords: wnt signaling, 4-helix bundle, extracellular domain, vascularization, blood-brain barrier, maltose-binding protein, signaling protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 1
• Total formula weight: 49757.74

Authors

Chang, T.H.,Hsieh, F.L.,Gabelli, S.B.,Nathans, J. (deposition date: 2020-03-26, release date: 2020-06-17, Last modification date: 2024-10-23)

Primary citation

Chang, T.H.,Hsieh, F.L.,Smallwood, P.M.,Gabelli, S.B.,Nathans, J.
Structure of the RECK CC domain, an evolutionary anomaly.
Proc.Natl.Acad.Sci.USA, 117:15104-15111, 2020

PubMed Abstract: Five small protein domains, the CC-domains, at the N terminus of the RECK protein, play essential roles in signaling by WNT7A and WNT7B in the context of central nervous system angiogenesis and blood-brain barrier formation and maintenance. We have determined the structure of CC domain 4 (CC4) at 1.65-Å resolution and find that it folds into a compact four-helix bundle with three disulfide bonds. The CC4 structure, together with homology modeling of CC1, reveals the surface locations of critical residues that were shown in previous mutagenesis studies to mediate GPR124 binding and WNT7A/WNT7B recognition and signaling. Surprisingly, sequence and structural homology searches reveal no other cell-surface or secreted domains in vertebrates that resemble the CC domain, a pattern that is in striking contrast to other ancient and similarly sized domains, such as Epidermal Growth Factor, Fibronectin Type 3, Immunoglobulin, and Thrombospondin type 1 domains, which are collectively present in hundreds of proteins.

PubMed: 32541044
DOI: 10.1073/pnas.2006332117

Experimental method

X-RAY DIFFRACTION (1.651 Å)