9DFT
G1 domain of human aggrecan
Summary for 9DFT
| Entry DOI | 10.2210/pdb9dft/pdb |
| Related | 9DFF |
| Descriptor | Aggrecan core protein, 2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION (3 entities in total) |
| Functional Keywords | extracellular matrix, hyaluronan, chondroitin sulfate proteoglycan, sugar binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 75619.17 |
| Authors | Bouyains, S. (deposition date: 2024-08-30, release date: 2025-04-30, Last modification date: 2025-06-11) |
| Primary citation | Otsuka, M.Y.,Essel, L.B.,Sinha, A.,Nickerson, G.,Mejia, S.M.,Edge, A.,Matthews, R.T.,Bouyain, S. Aggrecan immobilizes to perineuronal nets through hyaluronan-dependent and hyaluronan-independent binding activities. J.Biol.Chem., 301:108525-108525, 2025 Cited by PubMed Abstract: Aggrecan (ACAN) is a large, secreted chondroitin sulfate proteoglycan that includes three globular regions named G1, G2, G3, and is decorated with multiple glycosaminoglycan attachments between its G2 and G3 domains. The N-terminal G1 region interacts with the glycosaminoglycan hyaluronan (HA), which is an essential component of the vertebrate extracellular matrix. In the central nervous system, ACAN is found in perineuronal nets (PNNs), honeycomb-like structures that localize to the surface of parvalbumin-positive neurons in specific neural circuits. PNNs regulate the plasticity of the central nervous system, and it is believed that association between ACAN and HA is a foundational event in the assembly of these reticular structures. Here, we report the co-crystal structure of the G1 region of ACAN in the absence and presence of a HA decasaccharide and analyze the importance of the HA-binding activity of ACAN for its integration into PNNs. We demonstrate that the single immunoglobulin domain and the two Link modules that comprise the G1 region form a single structural unit, and that HA is clamped inside a groove that spans the length of the tandem Link domains. Introducing point mutations in the glycosaminoglycan-binding site eliminates HA-binding activity in ACAN, but, surprisingly, only decreases the integration of ACAN into PNNs. Thus, these results suggest that ACAN can be recruited into PNNs independently of its HA-binding activity. PubMed: 40273987DOI: 10.1016/j.jbc.2025.108525 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.5 Å) |
Structure validation
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