Advanced

Biosynthesis, processing, and sorting of human myeloperoxidase.

Hansson, Markus LU ; Olsson, Inge LU and Nauseef, William M (2006) In Archives of Biochemistry and Biophysics 445(2). p.214-224
Abstract
Exclusively synthesized by normal neutrophil and monocyte precursor cells, myeloperoxidase (MPO) functions not only in host defense by mediating efficient microbial killing but also can contribute to progressive tissue damage in chronic inflammatory states Such as atherosclerosis. The biosynthetic precursor, apoproMPO, is processed slowly in the ER, undergoing cotranslational N-glycosylation, transient interactions with the molecular chaperones calreticulin and calnexin, and heme incorporation to generate enzymatically active proMPO that is competent for export into the Golgi. After exiting the Golgi the propeptide is removed prior to final proteolytic processing in azurophil granules, resulting in formation of a symmetric MPO homodimer... (More)
Exclusively synthesized by normal neutrophil and monocyte precursor cells, myeloperoxidase (MPO) functions not only in host defense by mediating efficient microbial killing but also can contribute to progressive tissue damage in chronic inflammatory states Such as atherosclerosis. The biosynthetic precursor, apoproMPO, is processed slowly in the ER, undergoing cotranslational N-glycosylation, transient interactions with the molecular chaperones calreticulin and calnexin, and heme incorporation to generate enzymatically active proMPO that is competent for export into the Golgi. After exiting the Golgi the propeptide is removed prior to final proteolytic processing in azurophil granules, resulting in formation of a symmetric MPO homodimer linked by a disulfide bond. Some proMPO escapes granule targeting and becomes constitutively secreted to the extracellular environment. Although the precise mechanism is Unknown, the pro-segirient is required for normal processing and targeting. as propeptide-deleted MPO precursor is either degraded or constitutively secreted. Characterizing the molecular consequences of naturally Occurring mutations that cause inherited MPO deficiency provides unique insight into the structural determinants of MPO involved in biosynthesis, processing and targeting. (C) 2005 Elsevier Inc. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
inflammation, secretion, intracellular sorting, neutrophil, monocyte, calreticulin, calnexin, heme, lysosome, innate immunity
in
Archives of Biochemistry and Biophysics
volume
445
issue
2
pages
214 - 224
publisher
Academic Press
external identifiers
  • wos:000234961500003
  • pmid:16183032
  • scopus:30544452175
ISSN
0003-9861
DOI
10.1016/j.abb.2005.08.009
language
English
LU publication?
yes
id
41022222-a3c8-4573-838d-f96a529d249c (old id 143445)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16183032&dopt=Abstract
date added to LUP
2007-07-09 12:42:47
date last changed
2019-08-14 01:43:04
@article{41022222-a3c8-4573-838d-f96a529d249c,
  abstract     = {Exclusively synthesized by normal neutrophil and monocyte precursor cells, myeloperoxidase (MPO) functions not only in host defense by mediating efficient microbial killing but also can contribute to progressive tissue damage in chronic inflammatory states Such as atherosclerosis. The biosynthetic precursor, apoproMPO, is processed slowly in the ER, undergoing cotranslational N-glycosylation, transient interactions with the molecular chaperones calreticulin and calnexin, and heme incorporation to generate enzymatically active proMPO that is competent for export into the Golgi. After exiting the Golgi the propeptide is removed prior to final proteolytic processing in azurophil granules, resulting in formation of a symmetric MPO homodimer linked by a disulfide bond. Some proMPO escapes granule targeting and becomes constitutively secreted to the extracellular environment. Although the precise mechanism is Unknown, the pro-segirient is required for normal processing and targeting. as propeptide-deleted MPO precursor is either degraded or constitutively secreted. Characterizing the molecular consequences of naturally Occurring mutations that cause inherited MPO deficiency provides unique insight into the structural determinants of MPO involved in biosynthesis, processing and targeting. (C) 2005 Elsevier Inc. All rights reserved.},
  author       = {Hansson, Markus and Olsson, Inge and Nauseef, William M},
  issn         = {0003-9861},
  keyword      = {inflammation,secretion,intracellular sorting,neutrophil,monocyte,calreticulin,calnexin,heme,lysosome,innate immunity},
  language     = {eng},
  number       = {2},
  pages        = {214--224},
  publisher    = {Academic Press},
  series       = {Archives of Biochemistry and Biophysics},
  title        = {Biosynthesis, processing, and sorting of human myeloperoxidase.},
  url          = {http://dx.doi.org/10.1016/j.abb.2005.08.009},
  volume       = {445},
  year         = {2006},
}