Abstract
We have used affinity panning of libraries of bacteriophages that display random octapeptide or dodecapeptide sequences at the N-terminus of the adsorption protein (plll) to characterize peptides that bind to the endoplasmic reticulum chaperone BiP and to develop a scoring system that predicts potential BiP-binding sequences in naturally occurring polypeptides. BiP preferentially binds peptides containing a subset of aromatic and hydrophobic amino acids in alternating positions, suggesting that peptides bind in an extended conformation, with the side chains of alternating residues pointing into a cleft on the BiP molecule. Synthetic peptides with sequences corresponding to those displayed by BiP-binding bacteriophages bind to BiP and stimulate its ATPase activity, with a half-maximal concentration in the range 10-60 μM.
| Original language | English |
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| Pages (from-to) | 717-728 |
| Number of pages | 12 |
| Journal | Cell |
| Volume | 75 |
| Issue number | 4 |
| DOIs | |
| State | Published - Nov 19 1993 |
Funding
We thank Greg Flynn for the kind gift of bovine BiP. Anagha Sant and Maya Palnitkar for performing DNA sequencing, Lynn DeOgnyfor help with preparation and methylation of peptides, and Cynthia Hauser for invaluable assistance with the calculations and with preparation of figures. This work was funded in part by grants from the National Institutes of Health to M.J. H. G. and J. F. S. S. B.-E. was initially supported by an European Molecular Biology Organization postdoctoral fellowship.
| Funders |
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| European Molecular Biology Laboratory |