title: Prothymosin alpha: a biologically active protein with random coil conformation.
abstract: Prothymosin is an acidic protein with an unusual amino acid composition. Though its exact function is not yet known, its high evolutionary conservation and wide tissue distribution suggest an essential biological role. Its physical state, which is controversially discussed in previous publications, was investigated using small-angle X-ray scattering, dynamic light scattering, mass spectrometry, and circular dichroism (CD). Our results unequivocally demonstrate that prothymosin is a monomer under physiological conditions. The protein adopts a random coillike conformation but exhibits persistence of direction and curvature. No regular secondary structure is detectable by CD. The Stokes radius, Rs = 3.07 nm, and the radius of gyration, RG = 4.76 nm, are 1.77 and 3.42 times larger, respectively, than those expected for a compactly folded protein consisting of 109 amino acid residues. A remarkable amount of secondary structure is formed only in the presence of trifluoroethanol at low pH. The finding that a biologically active protein molecule with 109 amino acid residues adopts a random coil conformation under physiological conditions raises the question whether this is a rare or a hitherto-overlooked but widespread phenomenon in the field of macromolecular polypeptides.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Gast
authors.forename: H
authors.initials: H
authors.lastname: Damaschun
authors.forename: K
authors.initials: K
authors.lastname: Eckert
authors.forename: K
authors.initials: K
authors.lastname: Schulze-Forster
authors.forename: H R
authors.initials: HR
authors.lastname: Maurer
authors.forename: M
authors.initials: M
authors.lastname: Müller-Frohne
authors.forename: D
authors.initials: D
authors.lastname: Zirwer
authors.forename: J
authors.initials: J
authors.lastname: Czarnecki
authors.forename: G
authors.initials: G
authors.lastname: Damaschun
mesh_terms: D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D011498:Protein Precursors / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012542:Scattering, Radiation; D013947:Thymosin / Q000031:analogs & derivatives* / Q000737:chemistry; D013950:Thymus Gland / Q000201:enzymology
chemical_list: D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin