Computational design of peptides that target transmembrane helices

Hang Yin; Joanna S. Slusky; Bryan W. Berger; Robin S. Walters; Gaston Vilaire; Rustem I. Litvinov; James D. Lear; Gregory A. Caputo; Joel S. Bennett; William F. DeGrado

doi:10.1126/science.1136782

Computational design of peptides that target transmembrane helices

Hang Yin, Joanna S. Slusky, Bryan W. Berger, Robin S. Walters, Gaston Vilaire, Rustem I. Litvinov, James D. Lear, Gregory A. Caputo, Joel S. Bennett, William F. DeGrado

Research output: Contribution to journal › Article › peer-review

252 Scopus citations

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 (α_IIbβ₃ and (α _vβ₃) 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.

Original language	English (US)
Pages (from-to)	1817-1822
Number of pages	6
Journal	Science
Volume	315
Issue number	5820
DOIs	https://doi.org/10.1126/science.1136782
State	Published - Mar 30 2007
Externally published	Yes

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10.1126/science.1136782

Cite this

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title = "Computational design of peptides that target transmembrane helices",

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 (αIIbβ3 and (α vβ3) 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.",

author = "Hang Yin and Slusky, {Joanna S.} and Berger, {Bryan W.} and Walters, {Robin S.} and Gaston Vilaire and Litvinov, {Rustem I.} and Lear, {James D.} and Caputo, {Gregory A.} and Bennett, {Joel S.} and DeGrado, {William F.}",

year = "2007",

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doi = "10.1126/science.1136782",

language = "English (US)",

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TY - JOUR

T1 - Computational design of peptides that target transmembrane helices

AU - Yin, Hang

AU - Slusky, Joanna S.

AU - Berger, Bryan W.

AU - Walters, Robin S.

AU - Vilaire, Gaston

AU - Litvinov, Rustem I.

AU - Lear, James D.

AU - Caputo, Gregory A.

AU - Bennett, Joel S.

AU - DeGrado, William F.

PY - 2007/3/30

Y1 - 2007/3/30

N2 - 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 (αIIbβ3 and (α vβ3) 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.

AB - 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 (αIIbβ3 and (α vβ3) 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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Computational design of peptides that target transmembrane helices

Abstract

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