title: The human cardiac hormone fragment N-terminal pro B-type natriuretic peptide is an intrinsically unstructured protein.
abstract: The cardiac hormone B-type natriuretic peptide (BNP) is synthesized as a prepro 134 residue molecule which is further proteolytically processed into a 76 residue fragment termed N-terminal proBNP (NT-proBNP) and the active portion of this hormone, a 32-residue disulfide-linked peptide (BNP-32). The active hormone regulates cardiac hemodynamic output while as yet no biological function has been attributed to NT-proBNP. Some solution properties of synthetically generated NT-proBNP in benign media are known. The protein is monomeric, elutes aberrantly on size-exclusion chromatography as an apparent larger molecular species, and possesses little global secondary structure as assessed by circular dichroism. To explore the solution structure of NT-proBNP in greater detail, we use 2D-NOESY and 2D-TOCSY NMR on recombinant NT-proBNP to obtain a high resolution solution conformation at the alpha-carbon level. Importantly, NH(i)-NH(i+1) coupling is virtually absent at room temperature implying that large stretches of primary sequence are unordered. Together, the results of these physicochemical measurements classify NT-proBNP as a naturally unfolded protein referred to as an Intrinsically Unstructured Protein (IUP). The calculations of FoldIndex, a computer program which predicts disorder, were compared to the experimental results described here for NT-proBNP in addition to proBNP. NT-proBNP thus appears to be an ideal candidate for the study of native, unfolded proteins.
authors.affiliation: Department of Pathology and Immunology, Division of Laboratory Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Crimmins
authors.forename: Jeffrey L-F
authors.initials: JL
authors.lastname: Kao
mesh_terms: D019295:Computational Biology; D006801:Humans; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain