Atomic structure of a tryptophan-zipper pentamer
- *Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021; and †Department of Chemistry, New York University, New York, NY 10003
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Edited by William F. DeGrado, University of Pennsylvania School of Medicine, Philadelphia, PA, and approved October 6, 2004 (received for review July 22, 2004)
Abstract
Coiled-coil motifs are ubiquitous mediators of specific protein-protein interactions through the formation of interlocking hydrophobic seams between α-helical chains. Residues that form these seams occur at the first (a) and fourth (d) positions of a characteristic 7-aa repeat and are primarily aliphatic. The potential of aromatic residues to promote helix association in a coiled coil was explored by engineering a “Trp-zipper” protein with Trp residues at all 14 a and d positions. The protein forms a discrete, stable, α-helical pentamer in water at physiological pH. Its 1.45-Å crystal structure reveals a parallel, five-stranded coiled coil, a previously uncharacterized type of “knobs-into-holes” packing interaction between interfacial Trp side chains, and an unusual ≈8-Å-diameter axial channel lined with indole rings that is filled with polyethylene glycol 400 and water and sulfate ion molecules. The engineered Trp-zipper pentamer enlarges current views of coiled-coil assembly, molecular recognition, and protein engineering, and may serve as a soluble model for membrane ion channels.
Footnotes
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↵ ‡ To whom correspondence should be addressed at: Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021. E-mail: mlu{at}med.cornell.edu.
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This paper was submitted directly (Track II) to the PNAS office.
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Abbreviations: PEG, polyethylene glycol; GdmCl, guanidinium chloride.
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Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 1T8Z).
- Copyright © 2004, The National Academy of Sciences
