Cover Picture: Proteomics 23'10

Abstract

AbstractForks in the road to sobriety for outer membrane protein G (OmpG) under tensionMost work on protein unfolding and refolding has been done by shifting solution properties – pH, temperature, detergents, denaturants, salts, etc. Changing such bulk properties generally yields a simple two‐state model for renaturation – folded or unfolded. Unfolding by pulling at a single point on a tethered molecule with an atomic force microscope tip – single‐molecule force spectroscopy – allowed Damaghi et al. to map the forces required and the distances between the folded and unfolded states in much more detail. The OmpG molecule of E. coli is a barrel‐shaped transporter, comprising seven β‐hairpins. For hairpins I to IV the initial unfolding path steps are identical, then diverge as things become more complex, finally meeting again just before the last step. The rigidity of the pathways may be due in part to breaking up of an associated hydrogen bond array. An interesting benefit of the complexity is that it allows the separate evolution of the β‐loops for optimal function.Damaghi, M. et al., Proteomics 2010, 10, 4151–4162.Metering lights for the Translational Express?If you've driven on almost any urban American freeway (ha!) you have seen the signal lights that “meter” the traffic from the side roads onto the main highways. The genetic analogy is regulation of translational speed (red light time) through the choice of codons for multi‐codon amino acids. It has been observed that the faster codons appear more frequently in regions of mRNAs that tend to be susceptible to translational errors. The errors frequently take the form of protein aggregation. Lee et al. examined the effect quantitatively, looking at various types of amino acids, hidden and exposed, polar and hydrophobic, in five different organisms. There was no clear‐cut answer, but suggestions that it may be a way of reducing aggregation at functional sites by speeding up the translation rate to get past “sticky spots”.Lee, Y. et al., Proteomics 2010, 10, 4163–4171.A dictionary of ambiguities and singularitiesWe normally think of dictionaries as a source of truth, the ultimate arbiter of meaning and etymology. Now we face an ambiguous dictionary, one that lists only words up to six letters long but possibly with dozens of origins. Askenazi et al. have compiled a valuable reference that addresses a common problem for proteomics labs sequencing proteins from the bottom up: “How many different proteins could this peptide have come from?” They have built a service to answer the question. About every six months they aggregate ∼10 million protein sequences with their identifying information and connect the information to a rapid search software package (Pep2Pro). Test runs revealed that unique peptides can be found in a matter of seconds.Askenazi, M. et al., Proteomics 2010, 10, 4306–4310.