Effects of magnesium ions on recombinant human furin: Selective activation of hydrolytic activity upon substrates derived from virus envelope glycoprotein
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AbstractHere we report a detailed analysis of magnesium (Mg2+) ion effects on furin hydrolysis of fluorescent resonance energy transfer decapeptide substrates derived from canonical R-X-K/R-R furin cleavage motifs within certain viral envelope glycoproteins and eukaryotic proproteins. Using virus-derived sequences a selective activation of furin by Mg2+ ions was observed as a result of cooperativity between furin subsites. Furin hydrolysis of the peptides Abz-SRRHKR?FAGV-Q-EDDnp (from measles virus fusion protein Fo) and Abz-RERRRKKR?GLFG-Q-EDDnp (from Asian avian influenza A, H5N1) was activated between 60-and 80-fold by MgCl 2. It appears that virus envelope glycoprotein mutations have been selected to increase their susceptibility to furin within cells, a location where Mg2+ is present in adequate concentrations for activation. Both the pH profile of furin and its intrinsic fluorescence were modified by Mg 2+ ions, which bind to furin with a Kd value of 1.1 mm.
SponsorsConselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-77957605073&doi=10.1515%2fBC.2010.114&partnerID=40&md5=2db9b684a71c6ee16b981eb6d1f82490; http://hdl.handle.net/10713/12431
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