2M2F
The membran-proximal domain of ADAM17
Summary for 2M2F
| Entry DOI | 10.2210/pdb2m2f/pdb |
| NMR Information | BMRB: 18912 |
| Descriptor | Disintegrin and metalloproteinase domain-containing protein 17 (1 entity in total) |
| Functional Keywords | adam17, membrane-proximal domain, hydrolase regulator, closed conformer |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: P78536 |
| Total number of polymer chains | 1 |
| Total formula weight | 9905.12 |
| Authors | Duesterhoeft, S.,Jung, S.,Hung, C.,Tholey, A.,Soennichsen, F.D.,Groetzinger, J.,Lorenzen, I. (deposition date: 2012-12-20, release date: 2013-04-10, Last modification date: 2024-11-06) |
| Primary citation | Dusterhoft, S.,Jung, S.,Hung, C.W.,Tholey, A.,Sonnichsen, F.D.,Grotzinger, J.,Lorenzen, I. Membrane-proximal domain of a disintegrin and metalloprotease-17 represents the putative molecular switch of its shedding activity operated by protein-disulfide isomerase. J.Am.Chem.Soc., 135:5776-5781, 2013 Cited by PubMed Abstract: A disintegrin and metalloprotease-17 (ADAM17) is a major sheddase responsible for the regulation of a wide range of biological processes, like cellular differentiation, regeneration, or cancer progression. Hitherto, the mechanism regulating the enzymatic activity of ADAM17 is poorly understood. Recently, protein-disulfide isomerase (PDI) was shown to interact with ADAM17 and to down-regulate its enzymatic activity. Here we demonstrate by NMR spectroscopy and tandem-mass spectrometry that PDI directly interacts with the membrane-proximal domain (MPD), a domain of ADAM17 involved in its dimerization and substrate recognition. PDI catalyzes an isomerization of disulfide bridges within the thioredoxin motif C600XXC603 of the MPD and results in a drastic structural change between an active open state and an inactive closed conformation. This conformational change of the MPD putatively acts as a molecular switch, facilitating a global reorientation of the extracellular domains in ADAM17 and regulating its shedding activity. PubMed: 23521534DOI: 10.1021/ja400340u PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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