title: Transmembrane glycine zippers: physiological and pathological roles in membrane proteins.
abstract: 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-beta 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.
authors.affiliation: Department of Chemistry and Biochemistry and UCLA-DOE Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095, USA.
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Jeon
authors.forename: Amit
authors.initials: A
authors.lastname: Oberai
authors.forename: Duan
authors.initials: D
authors.lastname: Yang
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Schmidt
authors.forename: James U
authors.initials: JU
authors.lastname: Bowie
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics* / Q000502:physiology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics; D005998:Glycine / Q000235:genetics*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D007473:Ion Channels; D008565:Membrane Proteins; D005998:Glycine