N-linked glycosylation modulates dimerization of protein disulfide isomerase family A member 2 (PDIA2)

Walker, Adam K., Soo, Kai Ying, Levina, Vita, Talbo, Gert H. and Atkin, Julie D. (2013) N-linked glycosylation modulates dimerization of protein disulfide isomerase family A member 2 (PDIA2). FEBS Journal, 280 1: 233-243. doi:10.1111/febs.12063


Author Walker, Adam K.
Soo, Kai Ying
Levina, Vita
Talbo, Gert H.
Atkin, Julie D.
Title N-linked glycosylation modulates dimerization of protein disulfide isomerase family A member 2 (PDIA2)
Journal name FEBS Journal   Check publisher's open access policy
ISSN 1742-464X
1742-4658
Publication date 2013-01-01
Year available 2012
Sub-type Article (original research)
DOI 10.1111/febs.12063
Open Access Status Not yet assessed
Volume 280
Issue 1
Start page 233
End page 243
Total pages 11
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Protein disulfide isomerase (PDI) family members are important enzymes for the correct folding and maturation of proteins that transit or reside in the endoplasmic reticulum (ER). The human PDI family comprises at least 19 members that differ in cell type expression, substrate specificity and post-translational modifications. PDI family A member 2 (PDIA2, previously known as PDIp) has a similar domain structure to prototypical PDI (also known as PDIA1), but the function and post-translational modifications of PDIA2 remain poorly understood. Unlike most PDI family members, PDIA2 contains three predicted N-linked glycosylation sites. By site-directed mutagenesis and enzymatic deglycosylation, we show here that all three Asn residues within the potential N-linked glycosylation sites of human PDIA2 (N127, N284 and N516) are glycosylated in human cells. Furthermore, mutation of N284 to glycosylation-null Gln increases formation of a highly stable disulfide-bonded PDIA2 dimer. Nevertheless, in HeLa cells, both wild-type and N127/284/516Q mutant PDIA2 proteins localize to the ER, but not the ER-Golgi intermediate compartment, suggesting that glycosylation is important for PDIA2 protein-protein interactions but not subcellular localization. Finally, we identified human major histocompatibility complex class 1 antigens (HLA-A,B,C) as potential binding partners of PDIA2, suggesting an involvement for PDIA2 in antigen presentation in addition to its previously described roles in autoimmunity and Parkinson's disease. These results further characterize this poorly defined member of the PDI family.
Keyword Dimerization
Endoplasmic reticulum
Glycosylation
Major histocompatibility complex
Protein disulfide isomerase
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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