Molecular insights into biogenesis of glycosylphosphatidylinositol anchor proteins

Yidan Xu, Guowen Jia, Tingting Li, Zixuan Zhou, Yitian Luo, Yulin Chao, Juan Bao, Zhaoming Su (), Qianhui Qu () and Dianfan Li ()
Additional contact information
Yidan Xu: University of CAS, Chinese Academy of Sciences (CAS)
Guowen Jia: Sichuan University
Tingting Li: University of CAS, Chinese Academy of Sciences (CAS)
Zixuan Zhou: Fudan University
Yitian Luo: University of CAS, Chinese Academy of Sciences (CAS)
Yulin Chao: Fudan University
Juan Bao: University of CAS, Chinese Academy of Sciences (CAS)
Zhaoming Su: Sichuan University
Qianhui Qu: Fudan University
Dianfan Li: University of CAS, Chinese Academy of Sciences (CAS)

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Eukaryotic cells are coated with an abundance of glycosylphosphatidylinositol anchor proteins (GPI-APs) that play crucial roles in fertilization, neurogenesis, and immunity. The removal of a hydrophobic signal peptide and covalent attachment of GPI at the new carboxyl terminus are catalyzed by an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human GPI-T at a global 2.53-Å resolution, revealing an equimolar heteropentameric assembly. Structure-based mutagenesis suggests a legumain-like mechanism for the recognition and cleavage of proprotein substrates, and an endogenous GPI in the structure defines a composite cavity for the lipid substrate. This elongated active site, stemming from the membrane and spanning an additional ~22-Å space toward the catalytic dyad, is structurally suited for both substrates which feature an amphipathic pattern that matches this geometry. Our work presents an important step towards the mechanistic understanding of GPI-AP biosynthesis.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-30250-6 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:13:y:2022:i:1:d:10.1038_s41467-022-30250-6

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

DOI: 10.1038/s41467-022-30250-6

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 ().