title: Fibrinogen has chaperone-like activity.
abstract: Partially or completely unfolded polypeptides are highly prone to aggregation due to nonspecific interactions between their exposed hydrophobic surfaces. Extracellular proteins are continuously subjected to stresses conditions, but the existence of extracellular chaperones remains largely unexplored. The results presented here demonstrate that one of the most abundant extracellular proteins, fibrinogen has chaperone-like activity. Fibrinogen can specifically bind to nonnative form of citrate synthase and inhibit its thermal aggregation and inactivation in an ATP-independent manner. Interestingly, fibrinogen maintains thermal-denatured luciferase in a refolding competent state allowing luciferase to be refolded in cooperation with rabbit reticulocyte lysate. Fibrinogen also inhibits fibril formation of yeast prion protein Sup35 (NM). Furthermore, fibrinogen rescues thermal-induced protein aggregation in the plasma of fibrinogen-deficient mice. Our studies demonstrate the chaperone-like activity of fibrinogen, which not only provides new insights into the extracellular chaperone protein system, but also suggests potential diagnostic and therapeutic approaches to fibrinogen-related pathological conditions.
authors.affiliation: National Engineering Laboratory for Anti-tumor Protein Therapeutics Tsinghua University, Beijing 100084, China.
authors.forename: Huadong
authors.initials: H
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
authors.forename: Yujie
authors.initials: Y
authors.lastname: Cui
authors.forename: Yingbo
authors.initials: Y
authors.lastname: He
authors.forename: Xing
authors.initials: X
authors.lastname: Zeng
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Ploplis
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
authors.forename: Yongzhang
authors.initials: Y
authors.lastname: Luo
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002950:Citrate (si)-Synthase / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry*; D006358:Hot Temperature; D006801:Humans; D049409:Luciferases, Firefly / Q000737:chemistry; D018832:Molecular Chaperones / Q000737:chemistry*; D010454:Peptide Termination Factors; D011328:Prions / Q000737:chemistry; D017510:Protein Folding; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry
chemical_list: D000682:Amyloid; D018832:Molecular Chaperones; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005340:Fibrinogen; D049409:Luciferases, Firefly; D002950:Citrate (si)-Synthase