Computational design of peptides that target transmembrane helices |
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| Authors: | Yin Hang Slusky Joanna S Berger Bryan W Walters Robin S Vilaire Gaston Litvinov Rustem I Lear James D Caputo Gregory A Bennett Joel S DeGrado William F |
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| Institution: | Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. |
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| Abstract: | 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 (alphaIIbbeta3 and alphavbeta3) 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. |
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