Computational design of peptides that target transmembrane helices.
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.
Yin
Hang
H
Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Slusky
Joanna S
JS
Berger
Bryan W
BW
Walters
Robin S
RS
Vilaire
Gaston
G
Litvinov
Rustem I
RI
Lear
James D
JD
Caputo
Gregory A
GA
Bennett
Joel S
JS
DeGrado
William F
WF
D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry*; D030562:Databases, Protein; D019281:Dimerization; D004926:Escherichia coli / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D052898:Optical Tweezers; D053495:Osteopontin / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry* / Q000378:metabolism; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013057:Spectrum Analysis
D039302:Integrin alphaVbeta3; D008051:Lipid Bilayers; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D053495:Osteopontin