A remote prolyl isomerization controls domain assembly via a hydrogen bonding network

Titelangaben

Weininger, Ulrich ; Jakob, Roman P. ; Eckert, Barbara ; Schweimer, Kristian ; Schmid, Franz X. ; Balbach, Jochen:
A remote prolyl isomerization controls domain assembly via a hydrogen bonding network.
In: Proceedings of the National Academy of Sciences of the United States of America. Bd. 106 (2009) Heft 30 . - 12335 -12340.
ISSN 1091-6490
DOI: https://doi.org/10.1073/pnas.0902102106

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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.