Glycan Activation of a Sheddase: Electrostatic Recognition between Heparin and proMMP-7
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Authors
Fulcher, Yan G.
Prior, Stephen H.
Masuko, Sayaka
Li, Lingyun
Pu, Dennis
Zhang, Fuming
Linhardt, Robert J.
Van Doren, Steven R.
Issue Date
2017-07-05
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Heparan sulfate proteoglycans activate the matrix metalloproteinase-7 zymogen (proMMP-7) and recruit it in order to shed proteins from cell surfaces. This occurs in uterine and mammary epithelia, bacterial killing, lung healing, and tumor cell signaling. Basic tracks on proMMP-7 recognize polyanionic heparin, according to nuclear magnetic resonance and mutations disruptive of maturation. Contacts and proximity measurements guided docking of a heparin octasaccharide to proMMP-7. The reducing end fits into a basic pocket in the pro-domain while the chain continues toward the catalytic domain. Another oligosaccharide traverses a basic swath remote on the catalytic domain and inserts its reducing end into a slot formed with the basic C terminus. This latter association appears to support allosteric acceleration of proteolysis. The modes of binding account for extended, heterogeneous assemblies of proMMP-7 with heparinoids during maturation and for bridging to pro-α-defensins and proteoglycans. These associations support proteolytic release of activities at epithelial cell surfaces.
Description
Structure, 25, 1100–1110
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Glycan Activation of a Sheddase: Electrostatic Recognition between Heparin and proMMP-7, Y. G. Fulcher, S. H. Prior, S. Masuko, L. Li, D. Pu, F. Zhang, R. J. Linhardt, S. R. Van Doren, Structure, 25, 1100–1110, 2017.
Publisher
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
18784186
9692126
9692126