Dataset Information

Molecular Stressors Engender Protein Connectivity Dysfunction through Aberrant N-Glycosylation of a Chaperone.

ABSTRACT: Stresses associated with disease may pathologically remodel the proteome by both increasing interaction strength and altering interaction partners, resulting in proteome-wide connectivity dysfunctions. Chaperones play an important role in these alterations, but how these changes are executed remains largely unknown. Our study unveils a specific N-glycosylation pattern used by a chaperone, Glucose-regulated protein 94 (GRP94), to alter its conformational fitness and stabilize a state most permissive for stable interactions with proteins at the plasma membrane. This "protein assembly mutation' remodels protein networks and properties of the cell. We show in cells, human specimens, and mouse xenografts that proteome connectivity is restorable by inhibition of the N-glycosylated GRP94 variant. In summary, we provide biochemical evidence for stressor-induced chaperone-mediated protein mis-assemblies and demonstrate how these alterations are actionable in disease.

SUBMITTER: Yan P

PROVIDER: S-EPMC7372946 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Molecular Stressors Engender Protein Connectivity Dysfunction through Aberrant N-Glycosylation of a Chaperone.

Yan Pengrong P Patel Hardik J HJ Sharma Sahil S Corben Adriana A Wang Tai T Panchal Palak P Yang Chenghua C Sun Weilin W Araujo Thais L TL Rodina Anna A Joshi Suhasini S Robzyk Kenneth K Gandu Srinivasa S White Julie R JR de Stanchina Elisa E Modi Shanu S Janjigian Yelena Y YY Hill Elizabeth G EG Liu Bei B Erdjument-Bromage Hediye H Neubert Thomas A TA Que Nanette L S NLS Li Zihai Z Gewirth Daniel T DT Taldone Tony T Chiosis Gabriela G

Cell reports 20200601 13

Stresses associated with disease may pathologically remodel the proteome by both increasing interaction strength and altering interaction partners, resulting in proteome-wide connectivity dysfunctions. Chaperones play an important role in these alterations, but how these changes are executed remains largely unknown. Our study unveils a specific N-glycosylation pattern used by a chaperone, Glucose-regulated protein 94 (GRP94), to alter its conformational fitness and stabilize a state most permiss ...[more]

PMID: 32610141

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Dataset Information

Molecular Stressors Engender Protein Connectivity Dysfunction through Aberrant N-Glycosylation of a Chaperone.

Publications

Molecular Stressors Engender Protein Connectivity Dysfunction through Aberrant N-Glycosylation of a Chaperone.

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