Alpha(E)C, the C-terminal extension of fibrinogen, has chaperone-like activity.
Human fibrinogen is an important coagulation factor as well as an acute phase protein in the circulatory system. Fibrinogen-420 is distinguished from the conventional alpha chain of fibrinogen-340 by the presence of an additional 236-residue carboxyl terminus globular domain (alpha(E)C). The alpha(E)C domain of human fibrinogen-420 is a stable and early proteolytic cleavage product in the circulation. A genuine physiological function for alpha(E)C has not yet been established. Our study aims to characterize the novel chaperone-like activity of alpha(E)C. alpha(E)C efficiently protects a series of model proteins from thermally induced aggregation. Furthermore, alpha(E)C specifically recognizes the partially denatured form instead of the native form of citrate synthase (CS) and potentially protects it from thermally induced inactivation. The protective effect may result from formation of soluble complexes between alpha(E)C and partially denatured CS as tested by size exclusion column and electron microscope. In addition, alpha(E)C can keep the partially denatured luciferase in a folding competent state and help it refold in cooperation with rabbit reticulocyte lysate (RRL). Furthermore, alpha(E)C can also form complexes with thermally stressed plasma proteins. Our findings reveal the novel function of alpha(E)C as a chaperone-like protein, which not only provides new insights into the extracellular chaperone system but also has implications on the physiological and pathological relevance of fibrinogen.
Tang
Huadong
H
National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084, China.
Fu
Yan
Y
Zhan
Shunli
S
Luo
Yongzhang
Y
D002850:Chromatography, Gel; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008854:Microscopy, Electron; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D011489:Protein Denaturation; D053719:Tandem Mass Spectrometry
D018832:Molecular Chaperones; D005340:Fibrinogen