| membrane channel | membrane protein structure | prion | transmembrane helix )
Sanguk Kim *, Tae-Joon Jeon , Amit Oberai *, Duan Yang *, Jacob J. Schmidt , and James U. Bowie *
*Department of Chemistry and Biochemistry and UCLA-DOE Institute for Genomics and Proteomics and Department of Bioengineering, University of California, Los Angeles, CA 90095
Edited by Donald M. Engelman, Yale University, New Haven, CT, and approved August 12, 2005 (received for review February 13, 2005)
We have observed a common sequence motif in membrane proteins, which we call a glycine zipper. Glycine zipper motifs are strongly overrepresented and conserved in membrane protein sequences, and mutations in glycine zipper motifs are deleterious to function in many cases. The glycine zipper has a significant structural impact, engendering a strong driving force for right-handed packing against a neighboring helix. Thus, the presence of a glycine zipper motif leads directly to testable structural hypotheses, particularly for a subclass of glycine zipper proteins that form channels. For example, we suggest that the membrane pores formed by the amyloid- peptide in vitro are constructed by glycine zipper packing and find that mutations in the glycine zipper motif block channel formation. Our findings highlight an important structural motif in a wide variety of normal and pathological processes.
Author contributions: S.K., T.-J.J., A.O., D.Y., J.J.S., and J.U.B. designed research; S.K., T.-J.J., A.O., and D.Y. performed research; T.-J.J., A.O., and D.Y. contributed new reagents/analytic tools; S.K., T.-J.J., A.O., D.Y., J.J.S., and J.U.B. analyzed data; and S.K., T.-J.J., J.J.S., and J.U.B. wrote the paper.
Present address: Department of Life Science, POSTECH, Pohang University of Science and Technology, Pohang, Kyung-Buk 790-784, Korea.
To whom correspondence should be addressed.