Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 30 November 2007:
Vol. 318. no. 5855, pp. 1458 - 1461
DOI: 10.1126/science.1144972
Prev | Table of Contents | Next

Reports

Direct Observation of Chaperone-Induced Changes in a Protein Folding Pathway

Philipp Bechtluft,1* Ruud G. H. van Leeuwen,2*{dagger} Matthew Tyreman,2* Danuta Tomkiewicz,1 Nico Nouwen,1{ddagger} Harald L. Tepper,2§ Arnold J. M. Driessen,1 Sander J. Tans2||

How chaperone interactions affect protein folding pathways is a central problem in biology. With the use of optical tweezers and all-atom molecular dynamics simulations, we studied the effect of chaperone SecB on the folding and unfolding pathways of maltose binding protein (MBP) at the single-molecule level. In the absence of SecB, we find that the MBP polypeptide first collapses into a molten globulelike compacted state and then folds into a stable core structure onto which several {alpha} helices are finally wrapped. Interactions with SecB completely prevent stable tertiary contacts in the core structure but have no detectable effect on the folding of the external {alpha} helices. It appears that SecB only binds to the extended or molten globulelike structure and retains MBP in this latter state. Thus during MBP translocation, no energy is required to disrupt stable tertiary interactions.

1 Department of Molecular Microbiology, Groningen Bio-molecular Sciences and Biotechnology Institute and the Zernike Institute for Advanced Materials, University of Groningen, Kerklaan 30, 9751 NN Haren, Netherlands.
2 FOM Institute for Atomic and Molecular Physics (AMOLF), Kruislaan 407, 1098 SJ Amsterdam, Netherlands.

* These authors contributed equally to this work.

{dagger} Present address: Philips Research, High Tech Campus 36, 5656 AE Eindhoven, Netherlands.

{ddagger} Present address: Laboratoire de Symbiosis Tropicales et Méditerranéennes TA A-82/J, Campus International de Baillarguet, 34398 Montpellier cedex 5, France.

§ Present address: McKinsey and Company, Amstel 344, 1017 AS Amsterdam, Netherlands.

|| To whom correspondence should be addressed. E-mail: tans{at}amolf.nl

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
N-glycans are direct determinants of CFTR folding and stability in secretory and endocytic membrane traffic.
R. Glozman, T. Okiyoneda, C. M. Mulvihill, J. M. Rini, H. Barriere, and G. L. Lukacs (2009)
J. Cell Biol. 184, 847-862
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)