title: Influence of serum proteins on conformation of prostate-specific antigen.
abstract: Partition behavior of prostate-specific antigen (PSA) was studied in aqueous Dextran-Ficoll two-phase system. It was found that the partitioning of PSA changed in the presence of other proteins, in particular, bovine serum albumin, human serum albumin, human transferrin, and human gamma-globulin. The partition coefficient of PSA in mixtures with increasing amounts of these proteins decreased along the S-shaped curve and dropped to essentially the same value at the 10(4)-10(5) protein: PSA molar ratio. Partition behavior of the above proteins was examined separately. Partition coefficient of a protein represents the protein solvent exposed residues; i.e., it reflects the 3D-structure of the protein in solution. Partition of binary protein mixtures reflects the interaction of the two proteins and therefore characterizes the PSA-induced conformational changes in a protein agent and the change in the PSA conformation induced by a protein agent. In other words, the protein effect on the partition behavior of free PSA may be explained by the effect of the non-specific PSA-protein interactions on PSA conformation. Formation of such PSA-protein encounter complexes was shown to be dominated by the electrostatic forces, since the efficiency of a given protein-agent to induce changes in the partition behavior of PSA was proportional to its absolute mean net charge. Furthermore, in agreement with the earlier hypothesis that the protein segments with increased dynamic propensities (i.e., 'discrete breathers') can be important for conformational transitions accompanying binding processes, our analysis of intrinsically disordered regions (IDR) in all the proteins examined showed that the propensity for intrinsic disorder is related to the PSA partition-modulating capability of the protein.
authors.affiliation: AnalizaDx Inc., Cleveland, OH 44114, USA.
authors.forename: O
authors.initials: O
authors.lastname: Fedotoff
authors.forename: L M
authors.initials: LM
authors.lastname: Mikheeva
authors.forename: A
authors.initials: A
authors.lastname: Chait
authors.forename: V N
authors.initials: VN
authors.lastname: Uversky
authors.forename: B Y
authors.initials: BY
authors.lastname: Zaslavsky
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000737:chemistry*; D002417:Cattle; D006801:Humans; D017430:Prostate-Specific Antigen / Q000737:chemistry*; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012997:Solvents; D014168:Transferrin / Q000737:chemistry; D005719:gamma-Globulins / Q000737:chemistry
chemical_list: D001798:Blood Proteins; D012709:Serum Albumin; D012997:Solvents; D014168:Transferrin; D005719:gamma-Globulins; D012710:Serum Albumin, Bovine; D017430:Prostate-Specific Antigen