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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.

SUBMITTER: Weininger U

PROVIDER: S-EPMC2718393 | biostudies-other | 2009 Jul

REPOSITORIES: biostudies-other

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

Weininger Ulrich U Jakob Roman P RP Eckert Barbara B Schweimer Kristian K Schmid Franz X FX Balbach Jochen J

Proceedings of the National Academy of Sciences of the United States of America 20090715 30

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 ...[more]

PMID: 19617535

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