Linked Life Data

20347046

Source:http://linkedlifedata.com/resource/pubmed/id/20347046

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-6-10
pubmed:abstractText
The mechanism, in molecular terms of protein quality control, specifically of how the cell recognizes and discriminates misfolded proteins, remains a challenge. In the secretory pathway the folding status of glycoproteins passing through the endoplasmic reticulum is marked by the composition of the N-glycan. The different glycoforms are recognized by specialized lectins. The folding sensor UGGT acts as an unusual molecular chaperone and covalently modifies the Man9 N-glycan of a misfolded protein by adding a glucose moiety and converts it to Glc1Man9 that rebinds the lectin calnexin. However, further links between the folding status of a glycoprotein and the composition of the N-glycan are unclear. There is little unequivocal evidence for other proteins in the ER recognizing the N-glycan and also acting as molecular chaperones. Nevertheless, based upon a few examples, we suggest that this function is carried out by individual proteins in several different complexes. Thus, calnexin binds the protein disulfide isomerase ERp57, that acts upon Glc1Man9 glycoproteins. In another example the protein disulfide isomerase ERdj5 binds specifically to EDEM (which is probably a mannosidase) and a lectin OS9, and reduces the disulfide bonds of bound glycoproteins destined for ERAD. Thus the glycan recognition is performed by a lectin and the chaperone function performed by a specific partner protein that can recognize misfolded proteins. We predict that this will be a common arrangement of proteins in the ER and that members of protein foldase families such as PDI and PPI will bind specifically to lectins in the ER. Molecular chaperones BiP and GRp94 will assist in the folding of proteins bound in these complexes as well as in the folding of non-glycoproteins.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Calnexin, http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/HSP70 Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Lectins, http://linkedlifedata.com/resource/pubmed/chemical/Mannosidases, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Molecular Chaperones, http://linkedlifedata.com/resource/pubmed/chemical/Polysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Protein Disulfide-Isomerases, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/glucose-regulated proteins, http://linkedlifedata.com/resource/pubmed/chemical/molecular chaperone GRP78
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1096-3634
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
500-11
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Protein quality control in the ER: the recognition of misfolded proteins.
pubmed:affiliation
Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't