Comparison of in vivo selection and rational design of heterodimeric coiled coils.

摘要: Summary Coiled coils are formed by 3%–5% of amino acids in proteins [10], and this abundance emphasizes the To investigate how electrostatic interactions restrict importance specific pairing. In addition to effects associations coiled coils, we improved a hetero- matching core polarity [11], packing [12], dimeric coil (WinZip-A1B1) vivo selection irregularities heptad repeats [13], pairing specificand, alternatively, rational design. Selection from ity is thought derive mainly balance ionic libraries encoding variable edge (g e) residues between neighboring helices. both natuenriched g/e ion pairs, but optimum selected het- ral designed two- three-helical erodimers unexpectedly retained two predicted repul- charge repulsions homooligomers that resive pairs. The best genetically lieved heterooligomers sufficient mediate dimer displayed similar thermodynamic stability [7, 14–16]. We call idea specificity as rationally with pre- PV hypothesis, an abbreviation reference name dicted pairs at all positions. This design Kim coworkers obligate hetdesigned pair, however, was less effective than erodimeric [14]. debest pair mediating dimeriza- fined title peptides identical tion vivo. Thus, except e g positions, where one sequence depend on context, complementary contains Lys other Glu. charges positions rationalize only frac- peptide (like pairs) forms stable hettion sequences form stable, erodimer vitro.