3QW9

Crystal structure of betaglycan ZP-C domain

Summary for 3QW9

• Entry DOI: 10.2210/pdb3qw9/pdb
• Descriptor: Transforming growth factor beta receptor type 3, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)][alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)][alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: cytokine receptor, immunoglobulin domain, zona pellucida, tgf-beta ligand co-receptor, protein polymerization
• Biological source: Rattus norvegicus (rat)
• Total number of polymer chains: 2
• Total formula weight: 42237.99

Authors

Lin, S.J.,Jardetzky, T.S. (deposition date: 2011-02-27, release date: 2011-04-06, Last modification date: 2020-07-29)

Primary citation

Lin, S.J.,Hu, Y.,Zhu, J.,Woodruff, T.K.,Jardetzky, T.S.
Structure of betaglycan zona pellucida (ZP)-C domain provides insights into ZP-mediated protein polymerization and TGF-{beta} binding.
Proc.Natl.Acad.Sci.USA, 108:5232-5236, 2011

PubMed Abstract: The zona pellucida (ZP) domain is a bipartite protein structural element comprised of ZP-N and ZP-C regions. Most notable for its ability to mediate protein polymerization, many ZP proteins polymerize and assemble into long fibrils that form specialized extracellular matrices. Other ZP proteins (namely, betaglycan and endoglin) do not polymerize but serve as important membrane coreceptors for ligands in the transforming growth factor-β (TGF-β) superfamily. Here, we present the 2.0-Å resolution crystal structure of the betaglycan ZP-C region in combination with a downstream region known as the external hydrophobic patch (EHP). Similar to the ZP-N region, the ZP-C region also adopts an immunoglobulin-like fold, despite sharing no sequence homology and possessing different disulfide linkages. The EHP region, which was previously thought to be external to the ZP region, is integral to the ZP-C domain and corresponds to the ZP-C G strand. Our structure also indicates that the critical maturation cleavage of ZP proteins, a process that activates nascent ZP proteins for polymerization, occurs within the immunoglobulin domain at the FG loop. Nonpolymerizing ZP proteins such as betaglycan and endoglin do not contain this cleavage site. Finally, our structure suggests that the AB loop and the convex surface pocket are regions important for TGF-β ligand binding.

PubMed: 21402931
DOI: 10.1073/pnas.1010689108

Experimental method

X-RAY DIFFRACTION (2 Å)