5AEJ
Crystal structure of human Gremlin-1
Summary for 5AEJ
| Entry DOI | 10.2210/pdb5aej/pdb |
| Descriptor | GREMLIN-1, SULFATE ION (3 entities in total) |
| Functional Keywords | signaling protein, signaling, gremlin, growth factors, inhibitor, cystine knot, extracellular signalling, dan family |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Secreted : O60565 |
| Total number of polymer chains | 4 |
| Total formula weight | 70332.73 |
| Authors | Kisonaite, M.,Hyvonen, M. (deposition date: 2015-08-31, release date: 2016-04-13, Last modification date: 2024-11-13) |
| Primary citation | Kisonaite, M.,Wang, X.,Hyvonen, M. Structure of Gremlin-1 and Analysis of its Interaction with Bmp-2. Biochem.J., 473:1593-, 2016 Cited by PubMed Abstract: Bone morphogenetic protein 2 (BMP-2) is a member of the transforming growth factor-β (TGF-β) signalling family and has a very broad biological role in development. Its signalling is regulated by many effectors: transmembrane proteins, membrane-attached proteins and soluble secreted antagonists such as Gremlin-1. Very little is known about the molecular mechanism by which Gremlin-1 and other DAN (differential screening-selected gene aberrative in neuroblastoma) family proteins inhibit BMP signalling. We analysed the interaction of Gremlin-1 with BMP-2 using a range of biophysical techniques, and used mutagenesis to map the binding site on BMP-2. We have also determined the crystal structure of Gremlin-1, revealing a similar conserved dimeric structure to that seen in other DAN family inhibitors. Measurements using biolayer interferometry (BLI) indicate that Gremlin-1 and BMP-2 can form larger complexes, beyond the expected 1:1 stoichiometry of dimers, forming oligomers that assemble in alternating fashion. These results suggest that inhibition of BMP-2 by Gremlin-1 occurs by a mechanism that is distinct from other known inhibitors such as Noggin and Chordin and we propose a novel model of BMP-2-Gremlin-1 interaction yet not seen among any BMP antagonists, and cannot rule out that several different oligomeric states could be found, depending on the concentration of the two proteins. PubMed: 27036124DOI: 10.1042/BCJ20160254 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.904 Å) |
Structure validation
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