BiP (for Binding Protein) is a molecular chaperone in eukaryotic cells; it prevents the “inappropriate association of potentially complementary surfaces”. Molecular chaperones bind to protein as it is being synthesized, and keep the protein in an unfolded state until synthesis is complete (the reasoning for this is because some proteins may need association between distant ends, and if the distant end isn’t formed yet, the protein may form an undesired (or nonfunctional) structure.)

The cartoon illustrates the problems we have with predicting protein folding; we can look at established trends and predict what the protein may look like, but the actual mechanism of folding is very much a magic “black box” still.

We do know, however, that molecular chaperones are the key to proper protein folding. These will bind and sometimes even use ATP to force the protein into the functional shape.

In the article we reviewed, the focus was to determine what the binding site of BiP was specific for; they determined that BiP has 4 hydrophobic “pockets” in its active site, each spaced so that every other amino acid would fit into a pocket.  Thus, a peptide segment with a sequence of eight AA’s, alternating hydrophobic and hydrophilic, would have the greatest affinity for BiP.

As a side note, they also noted that the nature of the hydrophilic residues between the pocket sites were important, as well.  For instance, a proline in position 7 would increase binding twelvefold; this is attributed to the fact that the hard kink induced by proline relieves steric hindrances from bulky hydrophobic residues nearby.