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 March 2007:
Vol. 315. no. 5820, pp. 1817 - 1822
DOI: 10.1126/science.1136782
Prev | Table of Contents | Next

Research Articles

Computational Design of Peptides That Target Transmembrane Helices

Hang Yin,1* Joanna S. Slusky,1* Bryan W. Berger,1 Robin S. Walters,1 Gaston Vilaire,2 Rustem I. Litvinov,3 James D. Lear,1 Gregory A. Caputo,1 Joel S. Bennett,2 William F. DeGrado1,4{dagger}

A variety of methods exist for the design or selection of antibodies and other proteins that recognize the water-soluble regions of proteins; however, companion methods for targeting transmembrane (TM) regions are not available. Here, we describe a method for the computational design of peptides that target TM helices in a sequence-specific manner. To illustrate the method, peptides were designed that specifically recognize the TM helices of two closely related integrins ({alpha}IIbß3 and {alpha}vß3) in micelles, bacterial membranes, and mammalian cells. These data show that sequence-specific recognition of helices in TM proteins can be achieved through optimization of the geometric complementarity of the target-host complex.

1 Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Hematology-Oncology Division, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Department of Cell and Developmental Biology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4 Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: wdegrado{at}mail.med.upenn.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Spatial Structure of the Dimeric Transmembrane Domain of the Growth Factor Receptor ErbB2 Presumably Corresponding to the Receptor Active State.
E. V. Bocharov, K. S. Mineev, P. E. Volynsky, Y. S. Ermolyuk, E. N. Tkach, A. G. Sobol, V. V. Chupin, M. P. Kirpichnikov, R. G. Efremov, and A. S. Arseniev (2008)
J. Biol. Chem. 283, 6950-6956
   Abstract »    Full Text »    PDF »
Transmembrane Domain Interactions Control Biological Functions of Neuropilin-1.
L. Roth, C. Nasarre, S. Dirrig-Grosch, D. Aunis, G. Cremel, P. Hubert, and D. Bagnard (2008)
Mol. Biol. Cell 19, 646-654
   Abstract »    Full Text »    PDF »
Transmembrane domains of the syndecan family of growth factor coreceptors display a hierarchy of homotypic and heterotypic interactions.
I. C. Dews and K. R. MacKenzie (2007)
PNAS 104, 20782-20787
   Abstract »    Full Text »    PDF »
High-resolution design of a protein loop.
X. Hu, H. Wang, H. Ke, and B. Kuhlman (2007)
PNAS 104, 17668-17673
   Abstract »    Full Text »    PDF »
Toward high-resolution prediction and design of transmembrane helical protein structures.
P. Barth, J. Schonbrun, and D. Baker (2007)
PNAS 104, 15682-15687
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

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