title: pH-induced folding of an apoptotic coiled coil.
abstract: Par-4 is a 38-kD protein pivotal to the apoptotic pathways of various cell types, most notably prostate cells and neurons, where it has been linked to prostate cancer and various neurodegenerative disorders including Alzheimer's and Huntington's diseases and HIV encephalitis. The C-terminal region of Par-4 is responsible for homodimerization and the ability of Par-4 to interact with proposed effector molecules. In this study, we show that the C-terminal 47 residues of Par-4 are natively unfolded at physiological pH and temperature. Evidence is rapidly accumulating that natively unfolded proteins play an important role in various cellular functions and signaling pathways, and that folding can often be induced on complexation with effector molecules or alteration of environment. Here we use primarily CD studies to show that changes in the environment, particularly pH and temperature, can induce the Par-4 C terminus to form a self-associated coiled coil.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA. kaushik_dutta@urmc.rochester.edu
authors.forename: K
authors.initials: K
authors.lastname: Dutta
authors.forename: A
authors.initials: A
authors.lastname: Alexandrov
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.forename: S M
authors.initials: SM
authors.lastname: Pascal
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000737:chemistry*; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D047908:Intracellular Signaling Peptides and Proteins; D015233:Models, Statistical; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013696:Temperature
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C101296:prostate apoptosis response-4 protein