Structure and Dynamics of N-Glycosylated Human Ribonuclease 1
Name
nihms-1607138.pdf
Description
Accepted version
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740.5 KB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Kilgore, Henry R
Latham, Andrew P
Ressler, Valerie T
Zhang, Bin
Raines, Ronald T
Date Issued
2020
Journal
Biochemistry
Publisher
American Chemical Society (ACS)
Version
Author's final manuscript
Abstract
Copyright © 2020 American Chemical Society. Glycosylation is a common modification that can endow proteins with altered physical and biological properties. Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88. We have produced the three individual glycoforms that display the core heptasaccharide, Man5GlcNAc2, and analyzed the structure of each glycoform by using small-angle X-ray scattering along with molecular dynamics simulations. The glycan on Asn34 is relatively compact and rigid, donates hydrogen bonds that "cap"the carbonyl groups at the C-terminus of an α-helix, and enhances protein thermostability. In contrast, the glycan on Asn88 is flexible and can even enter the enzymic active site, hindering catalysis. The N-glycosylation of Asn76 has less pronounced consequences. These data highlight the diverse behaviors of Man5GlcNAc2 pendants and provide a structural underpinning to the functional consequences of protein glycosylation.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1021/ACS.BIOCHEM.0C00191
