Transmembrane glycine zippers: physiological and pathological roles in membrane proteins.
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.
Kim
Sanguk
S
Department of Chemistry and Biochemistry and UCLA-DOE Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095, USA.
Jeon
Tae-Joon
TJ
Oberai
Amit
A
Yang
Duan
D
Schmidt
Jacob J
JJ
Bowie
James U
JU
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
D016229:Amyloid beta-Peptides; D007473:Ion Channels; D008565:Membrane Proteins; D005998:Glycine