5LFN
Crystal structure of human chondroadherin
Summary for 5LFN
| Entry DOI | 10.2210/pdb5lfn/pdb |
| Descriptor | Chondroadherin, CHLORIDE ION (3 entities in total) |
| Functional Keywords | chondroadherin, extracellular matrix, small leucine-rich repeat protein, cell adhesion |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 153342.80 |
| Authors | Ramisch, S.,Pramhed, A.,Logan, D.T. (deposition date: 2016-07-03, release date: 2016-12-28, Last modification date: 2024-10-16) |
| Primary citation | Ramisch, S.,Pramhed, A.,Tillgren, V.,Aspberg, A.,Logan, D.T. Crystal structure of human chondroadherin: solving a difficult molecular-replacement problem using de novo models. Acta Crystallogr D Struct Biol, 73:53-63, 2017 Cited by PubMed Abstract: Chondroadherin (CHAD) is a cartilage matrix protein that mediates the adhesion of isolated chondrocytes. Its protein core is composed of 11 leucine-rich repeats (LRR) flanked by cysteine-rich domains. CHAD makes important interactions with collagen as well as with cell-surface heparin sulfate proteoglycans and αβ integrins. The integrin-binding site is located in a region of hitherto unknown structure at the C-terminal end of CHAD. Peptides based on the C-terminal human CHAD (hCHAD) sequence have shown therapeutic potential for treating osteoporosis. This article describes a still-unconventional structure solution by phasing with de novo models, the first of a β-rich protein. Structure determination of hCHAD using traditional, though nonsystematic, molecular replacement was unsuccessful in the hands of the authors, possibly owing to a combination of low sequence identity to other LRR proteins, four copies in the asymmetric unit and weak translational pseudosymmetry. However, it was possible to solve the structure by generating a large number of de novo models for the central LRR domain using Rosetta and multiple parallel molecular-replacement attempts using AMPLE. The hCHAD structure reveals an ordered C-terminal domain belonging to the LRRCT fold, with the integrin-binding motif (WLEAK) being part of a regular α-helix, and suggests ways in which experimental therapeutic peptides can be improved. The crystal structure itself and docking simulations further support that hCHAD dimers form in a similar manner to other matrix LRR proteins. PubMed: 28045385DOI: 10.1107/S205979831601980X PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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