Sulfation of a FLAG tag mediated by SLC35B2 and TPST2 affects antibody recognition.

A FLAG tag consisting of DYKDDDDK is an epitope tag that is frequently and widely used to detect recombinant proteins of interest. In this study, we performed a CRISPR-based genetic screening to identify factors involved in the detection of a FLAG-tagged misfolded model protein at the cell surface....

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Main Authors: Xin-Yu Guo, Xiao-Dong Gao, Morihisa Fujita
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0250805&type=printable
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author Xin-Yu Guo
Xiao-Dong Gao
Morihisa Fujita
author_facet Xin-Yu Guo
Xiao-Dong Gao
Morihisa Fujita
author_sort Xin-Yu Guo
collection DOAJ
description A FLAG tag consisting of DYKDDDDK is an epitope tag that is frequently and widely used to detect recombinant proteins of interest. In this study, we performed a CRISPR-based genetic screening to identify factors involved in the detection of a FLAG-tagged misfolded model protein at the cell surface. In the screening, SLC35B2, which encodes 3'-phosphoadenosine-5'-phosphosulfate transporter 1, was identified as the candidate gene. The detection of FLAG-tagged misfolded proteins at the cell surface was significantly increased in SLC35B2-knockout cells. Furthermore, protein tyrosine sulfation mediated by tyrosyl-protein sulfotransferase 2 (TPST2) suppressed FLAG-tagged protein detection. Localization analysis of the FLAG-tagged misfolded proteins confirmed that defects in tyrosine sulfation are only responsible for enhancing anti-FLAG staining on the plasma membrane but not inducing the localization change of misfolded proteins on the plasma membrane. These results suggest that a FLAG tag on the misfolded protein would be sulfated, causing a reduced detection by the M2 anti-FLAG antibody. Attention should be required when quantifying the FLAG-tagged proteins in the secretory pathway.
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spelling doaj-art-9a25ed81827643de90cd70a9dda839522025-08-20T02:55:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01165e025080510.1371/journal.pone.0250805Sulfation of a FLAG tag mediated by SLC35B2 and TPST2 affects antibody recognition.Xin-Yu GuoXiao-Dong GaoMorihisa FujitaA FLAG tag consisting of DYKDDDDK is an epitope tag that is frequently and widely used to detect recombinant proteins of interest. In this study, we performed a CRISPR-based genetic screening to identify factors involved in the detection of a FLAG-tagged misfolded model protein at the cell surface. In the screening, SLC35B2, which encodes 3'-phosphoadenosine-5'-phosphosulfate transporter 1, was identified as the candidate gene. The detection of FLAG-tagged misfolded proteins at the cell surface was significantly increased in SLC35B2-knockout cells. Furthermore, protein tyrosine sulfation mediated by tyrosyl-protein sulfotransferase 2 (TPST2) suppressed FLAG-tagged protein detection. Localization analysis of the FLAG-tagged misfolded proteins confirmed that defects in tyrosine sulfation are only responsible for enhancing anti-FLAG staining on the plasma membrane but not inducing the localization change of misfolded proteins on the plasma membrane. These results suggest that a FLAG tag on the misfolded protein would be sulfated, causing a reduced detection by the M2 anti-FLAG antibody. Attention should be required when quantifying the FLAG-tagged proteins in the secretory pathway.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0250805&type=printable
spellingShingle Xin-Yu Guo
Xiao-Dong Gao
Morihisa Fujita
Sulfation of a FLAG tag mediated by SLC35B2 and TPST2 affects antibody recognition.
PLoS ONE
title Sulfation of a FLAG tag mediated by SLC35B2 and TPST2 affects antibody recognition.
title_full Sulfation of a FLAG tag mediated by SLC35B2 and TPST2 affects antibody recognition.
title_fullStr Sulfation of a FLAG tag mediated by SLC35B2 and TPST2 affects antibody recognition.
title_full_unstemmed Sulfation of a FLAG tag mediated by SLC35B2 and TPST2 affects antibody recognition.
title_short Sulfation of a FLAG tag mediated by SLC35B2 and TPST2 affects antibody recognition.
title_sort sulfation of a flag tag mediated by slc35b2 and tpst2 affects antibody recognition
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0250805&type=printable
work_keys_str_mv AT xinyuguo sulfationofaflagtagmediatedbyslc35b2andtpst2affectsantibodyrecognition
AT xiaodonggao sulfationofaflagtagmediatedbyslc35b2andtpst2affectsantibodyrecognition
AT morihisafujita sulfationofaflagtagmediatedbyslc35b2andtpst2affectsantibodyrecognition