title: A remote prolyl isomerization controls domain assembly via a hydrogen bonding network.
abstract: Prolyl cis/trans isomerizations determine the rates of protein folding reactions and can serve as molecular switches and timers. In the gene-3-protein of filamentous phage, Pro-213 trans --> cis isomerization in a hinge region controls the assembly of the 2 domains N1 and N2 and, in reverse, the activation of the phage for infection. We elucidated the structural and energetic basis of this proline-limited domain assembly at the level of individual residues by real-time 2D NMR. A local cluster of inter-domain hydrogen bonds, remote from Pro-213, is stabilized up to 3,000-fold by trans --> cis isomerization. This network of hydrogen bonds mediates domain assembly and is connected with Pro-213 by rigid backbone segments. Thus, proline cis/trans switching is propagated in a specific and directional fashion to change the protein structure and stability at a distant position.
authors.affiliation: Institut für Physik, Biophysik, and Mitteldeutsches Zentrum für Struktur und Dynamik der Proteine (MZP), Martin-Luther-Universität Halle-Wittenberg, D-06120 Halle(Saale), Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Weininger
authors.forename: Roman P
authors.initials: RP
authors.lastname: Jakob
authors.forename: Barbara
authors.initials: B
authors.lastname: Eckert
authors.forename: Kristian
authors.initials: K
authors.lastname: Schweimer
authors.forename: Franz X
authors.initials: FX
authors.lastname: Schmid
authors.forename: Jochen
authors.initials: J
authors.lastname: Balbach
mesh_terms: D000465:Algorithms; D017104:Bacteriophage M13 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D011392:Proline / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D014764:Viral Proteins; D011392:Proline; D019696:Peptidylprolyl Isomerase