PMID- 24223975
OWN - NLM
STAT- MEDLINE
DCOM- 20140818
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - Concerted in vitro trimming of viral HLA-B27-restricted ligands by human ERAP1 
      and ERAP2 aminopeptidases.
PG  - e79596
LID - 10.1371/journal.pone.0079596 [doi]
LID - e79596
AB  - In the classical human leukocyte antigen (HLA) class I antigen processing and 
      presentation pathway, the antigenic peptides are generated from viral proteins by 
      multiple proteolytic cleavages of the proteasome (and in some cases other 
      cytosolic proteases) and transported to the endoplasmic reticulum (ER) lumen 
      where they are exposed to aminopeptidase activity. In human cells, two different 
      ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues 
      of peptide precursors. In this study, the possible cooperative effect of 
      generating five naturally processed HLA-B27 ligands by both proteases was 
      analyzed. We identified differences in the products obtained with increased 
      detection of natural HLA-B27 ligands by comparing double versus single enzyme 
      digestions by mass spectrometry analysis. These in vitro data suggest that each 
      enzyme can use the degradation products of the other as a substrate for new 
      N-terminal trimming, indicating concerted aminoproteolytic activity of ERAP 1 and 
      ERAP2.
FAU - Lorente, Elena
AU  - Lorente E
AD  - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain.
FAU - Barriga, Alejandro
AU  - Barriga A
FAU - Johnstone, Carolina
AU  - Johnstone C
FAU - Mir, Carmen
AU  - Mir C
FAU - Jimenez, Mercedes
AU  - Jimenez M
FAU - Lopez, Daniel
AU  - Lopez D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131101
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (Ligands)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Viral Proteins)
RN  - EC 3.4.11.- (Aminopeptidases)
RN  - EC 3.4.11.- (ERAP1 protein, human)
RN  - EC 3.4.11.- (ERAP2 protein, human)
SB  - IM
MH  - Amino Acid Sequence
MH  - Aminopeptidases/chemistry/*metabolism
MH  - HLA-B27 Antigen/*metabolism
MH  - Humans
MH  - Ligands
MH  - Minor Histocompatibility Antigens
MH  - Molecular Sequence Data
MH  - Protein Multimerization
MH  - Protein Structure, Quaternary
MH  - *Proteolysis
MH  - Respiratory Syncytial Virus, Human/metabolism
MH  - Viral Proteins/chemistry/*metabolism
PMC - PMC3815102
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/14 06:00
MHDA- 2014/08/19 06:00
PMCR- 2013/11/01
CRDT- 2013/11/14 06:00
PHST- 2013/04/11 00:00 [received]
PHST- 2013/09/24 00:00 [accepted]
PHST- 2013/11/14 06:00 [entrez]
PHST- 2013/11/14 06:00 [pubmed]
PHST- 2014/08/19 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - PONE-D-13-14999 [pii]
AID - 10.1371/journal.pone.0079596 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 1;8(11):e79596. doi: 10.1371/journal.pone.0079596. eCollection 
      2013.