Pasala, C.; Sharma, S.; Roychowdhury, T.; Moroni, E.; Colombo, G.; Chiosis, G. N-Glycosylation as a Modulator of Protein Conformation and Assembly in Disease. Biomolecules2024, 14, 282.
Pasala, C.; Sharma, S.; Roychowdhury, T.; Moroni, E.; Colombo, G.; Chiosis, G. N-Glycosylation as a Modulator of Protein Conformation and Assembly in Disease. Biomolecules 2024, 14, 282.
Pasala, C.; Sharma, S.; Roychowdhury, T.; Moroni, E.; Colombo, G.; Chiosis, G. N-Glycosylation as a Modulator of Protein Conformation and Assembly in Disease. Biomolecules2024, 14, 282.
Pasala, C.; Sharma, S.; Roychowdhury, T.; Moroni, E.; Colombo, G.; Chiosis, G. N-Glycosylation as a Modulator of Protein Conformation and Assembly in Disease. Biomolecules 2024, 14, 282.
Abstract
Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations, characterized by distinct interactomes – namely protein assemblies - under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly and disease.
Keywords
N-glycosylation; disease; conformational mutant; aberrant protein assembly; energy landscape; SARS-CoV-2 spike protein; glucose regulated protein 94 (GRP94); prion protein; disease-associated protein conformation; protein dynamics; protein assembly mutation; gain-of-function conformational change
Subject
Biology and Life Sciences, Other
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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