Identification of a Golgi GPI-N-acetylgalactosamine transferase with tandem transmembrane regions in the catalytic domain

Tetsuya Hirata, Sushil K. Mishra, Shota Nakamura, Kazunobu Saito, Daisuke Motooka, Yoko Takada, Noriyuki Kanzawa, Yoshiko Murakami, Yusuke Maeda, Morihisa Fujita, Yoshiki Yamaguchi and Taroh Kinoshita ()
Additional contact information
Tetsuya Hirata: Osaka University
Sushil K. Mishra: RIKEN Global Research Cluster
Shota Nakamura: Osaka University
Kazunobu Saito: Osaka University
Daisuke Motooka: Osaka University
Yoko Takada: Osaka University
Noriyuki Kanzawa: Osaka University
Yoshiko Murakami: Osaka University
Yusuke Maeda: Osaka University
Morihisa Fujita: Jiangnan University
Yoshiki Yamaguchi: RIKEN Global Research Cluster
Taroh Kinoshita: Osaka University

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract Many eukaryotic proteins are anchored to the cell surface via the glycolipid glycosylphosphatidylinositol (GPI). Mammalian GPIs have a conserved core but exhibit diverse N-acetylgalactosamine (GalNAc) modifications, which are added via a yet unresolved process. Here we identify the Golgi-resident GPI-GalNAc transferase PGAP4 and show by mass spectrometry that PGAP4 knockout cells lose GPI-GalNAc structures. Furthermore, we demonstrate that PGAP4, in contrast to known Golgi glycosyltransferases, is not a single-pass membrane protein but contains three transmembrane domains, including a tandem transmembrane domain insertion into its glycosyltransferase-A fold as indicated by comparative modeling. Mutational analysis reveals a catalytic site, a DXD-like motif for UDP-GalNAc donor binding, and several residues potentially involved in acceptor binding. We suggest that a juxtamembrane region of PGAP4 accommodates various GPI-anchored proteins, presenting their acceptor residue toward the catalytic center. In summary, we present insights into the structure of PGAP4 and elucidate the initial step of GPI-GalNAc biosynthesis.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02799-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02799-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02799-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().