Arolas, Joan L; Broder, Claudia; Jefferson, Tamara; Guevara, Tibisay; Sterchi, Erwin E; Bode, Wolfram; Stöcker, Walter; Becker-Pauly, Christoph; Gomis-Rüth, F Xavier (2012). Structural basis for the sheddase function of human meprin β metalloproteinase at the plasma membrane. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 109(40), pp. 16131-6. Washington, D.C.: National Academy of Sciences NAS 10.1073/pnas.1211076109
Full text not available from this repository.Ectodomain shedding at the cell surface is a major mechanism to regulate the extracellular and circulatory concentration or the activities of signaling proteins at the plasma membrane. Human meprin β is a 145-kDa disulfide-linked homodimeric multidomain type-I membrane metallopeptidase that sheds membrane-bound cytokines and growth factors, thereby contributing to inflammatory diseases, angiogenesis, and tumor progression. In addition, it cleaves amyloid precursor protein (APP) at the β-secretase site, giving rise to amyloidogenic peptides. We have solved the X-ray crystal structure of a major fragment of the meprin β ectoprotein, the first of a multidomain oligomeric transmembrane sheddase, and of its zymogen. The meprin β dimer displays a compact shape, whose catalytic domain undergoes major rearrangement upon activation, and reveals an exosite and a sugar-rich channel, both of which possibly engage in substrate binding. A plausible structure-derived working mechanism suggests that substrates such as APP are shed close to the plasma membrane surface following an "N-like" chain trace.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
UniBE Contributor: |
Sterchi, Erwin-Ernst |
ISSN: |
0027-8424 |
Publisher: |
National Academy of Sciences NAS |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:37 |
Last Modified: |
05 Dec 2022 14:11 |
Publisher DOI: |
10.1073/pnas.1211076109 |
PubMed ID: |
22988105 |
Web of Science ID: |
000309611400042 |
URI: |
https://boris.unibe.ch/id/eprint/15034 (FactScience: 222188) |
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