Colicin crystal structures: pathways and mechanisms for colicin insertion into membranes

Abstract

The X-ray structures of the channel-forming colicins Ia and N, and endoribonucleolytic colicin E3, as well as of the channel domains of colicins A and E1, and spectroscopic and calorimetric data for intact colicin E1, are discussed in the context of the mechanisms and pathways by which colicins are imported into cells. The extensive helical coiled-coil in the R domain and internal hydrophobic hairpin in the C domain are important features relevant to colicin import and channel formation. The concept of outer membrane translocation mediated by two receptors, one mainly used for initial binding and second for translocation, such as BtuB and TolC, respectively, is discussed. Helix elongation and conformational flexibility are prerequisites for import of soluble toxin-like proteins into membranes. Helix elongation contradicts suggestions that the colicin import involves a molten globule intermediate. The nature of the open-channel structure is discussed.

Role and location of the unusual redox-active cysteines in the hydrophobic domain of the transmembrane electron transporter DsbD

“…Such a process would face a large energy barrier associated with translocation of charged residues across the membrane. However, this type of translocation is certainly conceivable because insertion of charged helices into a membrane and translocation of a water-soluble domain across planar phospholipid bilayers have already been reported for colicins and the diphtheria toxin, respectively (23,24). Our previous failure to find a mixed disulfide intermediate between ␤ and ␥ (10) may be due to its short-lived nature, a consequence of the unfavorable energy threshold required for this proposed interaction.…”

The N-Terminal Domain of Bcl-xL Reversibly Binds Membranes in a pH-Dependent Manner

“…Structurally, Bcl-x L ΔTM is most similar to the translocation domain of diphtheria toxin (23). For this toxin, as well as others, membrane association is mediated in part by the so-called hydrophobic, helical hairpin, which corresponds to α-helices 5 and 6 in Bcl-x L ΔTM (Figure 5a) (38)(39)(40)(41)(42)(43)(44)(45)(46). Despite the structural similarity, the sequences of these proteins are less than 19% identical, and they possibly are an example of convergent evolution toward a versatile protein fold.…”

The Bax pore in liposomes, Biophysics

“…24,27,[37][38][39] This hairpin is proposed to extend, thereby forming the handle of an umbrella with the remaining helices distributed on the insertion surface of the membrane. 40,41 Although these models only suggest events in membrane insertion, they have been used to develop the concept of activation of the soluble proapoptotic Bcl-2-family members.…”