Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Oligosaccharyltransferase (OST) catalyzes oligosaccharide transfer to the Asn residue in the N-glycosylation sequon, Asn-X-Ser/Thr, where Pro is strictly excluded at position X. Considering the unique structural properties of proline, this exclusion may not be surprising, but the structural basis for the rejection of Pro residues should be explained explicitly. Here we determined the crystal structure of an archaeal OST in a complex with a sequon-containing peptide and dolichol-phosphate to a 2.7 Å resolution. The sequon part in the peptide forms two inter-chain hydrogen bonds with a conserved amino acid motif, TIXE. We confirmed the essential role of the TIXE motif and the adjacent regions by extensive alanine-scanning of the external loop 5. A Ramachandran plot revealed that the ring structure of the Pro side chain is incompatible with the ϕ backbone dihedral angle around -150° in the rigid sequon-TIXE structure. The present structure clearly provides the structural basis for the exclusion of Pro residues from the N-glycosylation sequon.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342417 | PMC |
| http://dx.doi.org/10.1038/s42003-021-02473-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Protein β-O-glucosylation by Legionella LtpM through short consensus sequons G-T/S and S-G.
Nat Chem Biol
July 2025
College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
Unlike N-glycosylation, protein O-glycosylation often lacks a strict consensus sequon, making synthesis of homogeneous O-glycoproteins and site-specific engineering of O-glucosylation challenging. Here we identify Legionella effector LtpM as a versatile protein β-O-glucosyltransferase recognizing extremely short two-residue sequons G-T/S and S-G. X-ray crystallography, molecular simulation and biochemical studies together reveal a unique catalytic mechanism: four residues of LtpM (F166, Q167, W228 and K225) serve as 'gatekeepers' above the binding pocket of the uridine diphosphate (UDP)-glucose sugar donor to form a narrow clamp for the substrate proteins, limiting the residue adjacent to serine or threonine to be exclusively glycine.
View Article and Find Full Text PDFCampus-based genomic surveillance uncovers early emergence of a future dominant A(H3N2) influenza clade.
medRxiv
June 2025
The Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine and School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
We conducted genomic surveillance of seasonal influenza during the 2022-2023 northern hemisphere flu season on a large university setting in Southwest Arizona USA to understand the diversity, evolution, and spread within a local environment and how it relates to national data. Through high-throughput sequencing and bioinformatics, we identified 100 positive samples (19%) from 516 clinical swabs collected at the student health clinic. We observed a dominance of subtype A(H3N2) which was consistent nationally for the 2022-2023 season.
View Article and Find Full Text PDFCMP-sialic acid synthetase in Drosophila requires N-glycosylation of a noncanonical site.
J Biol Chem
June 2025
Department of Biochemistry and Biophysics, AgriLife Research, Texas A&M University, College Station, Texas, USA. Electronic address:
Sialylation plays important roles in animals, affecting numerous molecular and cell interactions. In Drosophila, sialylation regulates neural transmission and mediates communication between neurons and glia. Drosophila CMP-sialic acid synthetase (CSAS), a key enzyme of the sialylation pathway, is localized to the Golgi and modified by N-glycosylation, suggesting that this modification can affect CSAS function.
View Article and Find Full Text PDFN-glycosylation in the SERPIN domain of the C1-esterase inhibitor in hereditary angioedema.
JCI Insight
January 2025
Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, USA.
Hereditary angioedema is an autosomal dominant disorder caused by defects in C1-esterase inhibitor (C1-INH), resulting in poorly controlled activation of the kallikrein-kinin system and bradykinin overproduction. C1-INH is a heavily glycosylated protein in the serine protease inhibitor (SERPIN) family, yet the role of these glycosylation sites remains unclear. To elucidate the functional impact of N-glycosylation in the SERPIN domain of C1-INH, we engineered 4 sets consisting of 26 variants at or near the N-linked sequon (NXS/T).
View Article and Find Full Text PDFPhosphorylation of N-glycans in the brain: The case for a non-canonical pathway?
BBA Adv
December 2024
Genos Glycoscience Research Laboratory, Zagreb, Croatia.
Asparagine-linked glycosylation (N-glycosylation) is a common co- and post-translational modification that refers to the addition of complex carbohydrates, called N-linked glycans (N-glycans), to asparagine residues within defined sequons of polypeptide acceptors. Some N-glycans can be modified by the addition of phosphate moieties to their monosaccharide residues, thus forming phospho-N-glycans (PNGs). The most prominent such carbohydrate modification is mannose-6-phosphate (M6P) which plays a well-established role in trafficking of acid hydrolases to lysosomes.
View Article and Find Full Text PDF