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Glycan Activation of a Sheddase: Electrostatic Recognition between Heparin and proMMP-7.


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-?-defensins and proteoglycans. These associations support proteolytic release of activities at epithelial cell surfaces.

SUBMITTER: Fulcher YG 

PROVIDER: S-EPMC5526709 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Glycan Activation of a Sheddase: Electrostatic Recognition between Heparin and proMMP-7.

Fulcher Yan G YG   Prior Stephen H SH   Masuko Sayaka S   Li Lingyun L   Pu Dennis D   Zhang Fuming F   Linhardt Robert J RJ   Van Doren Steven R SR  

Structure (London, England : 1993) 20170622 7


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  ...[more]

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2019-12-10 | GSE141679 | GEO