TAILIEUCHUNG - Báo cáo khóa học: The role of N-linked glycosylation in the protection of human and bovine lactoferrin against tryptic proteolysis

Lactoferrin (LF) is an iron-binding glycoprotein of the innate host defence system. To elucidate the role ofN-linked glycosylation in protection of LF against proteolysis, we compared the tryptic susceptibility of human LF (hLF) variants from human milk, expressed in human 293(S) cells or in the milk of transgenic mice and cows. The analysis revealed that recombinant hLF (rhLF) with mutations Ile130fiThr and Gly404fiCys was about twofold more susceptible than glycosylated and unglycosylated variants with the naturally occurring Ile130 and Gly404 | Eur. J. Biochem. 271 678-684 2004 FEBS 2004 doi The role of N-linked glycosylation in the protection of human and bovine lactoferrin against tryptic proteolysis Harrie A. van Veen Marlieke E. J. Geerts Patrick H. C. van Berkel and Jan H. Nuijens Pharming Archimedesweg Leiden the Netherlands Lactoferrin LF is an iron-binding glycoprotein of the innate host defence system. To elucidate the role of N-linked glycosylation in protection of LF against proteolysis we compared the tryptic susceptibility of human LF hLF variants from human milk expressed in human 293 S cells or in the milk of transgenic mice and cows. The analysis revealed that recombinant hLF rhLF with mutations Ile130fiThr and Gly404fiCys was about twofold more susceptible than glycosylated and unglycosylated variants with the naturally occurring Ile130 and Gly404. Hence N-linked glycosylation is not involved in protection of hLF against tryptic proteolysis. Apparently the previously reported protection by N-linked glycosylation of hLF van Berkel . Geerts . van Veen . Kooiman . Pieper F. de Boer . Nuijens . 1995 Biochem. J. 312 107-114 is restricted to rhLF containing the Thr130 and Cys404. Comparison of the tryptic proteolysis of hLF and bovine LF bLF revealed that hLF is about 100-fold more resistant than bLF. Glycosylation variants A and B of bLF differed by about 10-fold in susceptibility to trypsin. This difference is due to glycosylation at Asn281 in bLF-A. Hence glycosylation at Asn281 protects bLF against cleavage by trypsin at Lys282. Keywords lactoferrin tryptic susceptibility N-linked glycosylation transgenic gastrointestinal. Lactoferrin LF is a metal-binding glycoprotein of Mr 77 000 that belongs to the transferrin family 1 . The molecule is found in secretions such as milk tears and saliva but also in the secondary granules of neutrophils reviewed in 2 . LF is involved in nonspecific host defence against infection and severe inflammation

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• oxidation
• Crystal structure
• bacteria
• medical knowledge
• medical research
• analysis of cytoplasmic
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine