| Autor: |
Kreitler DF; Department of Chemistry , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States., Yao Z; Graduate Program in Biophysics , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States., Steinkruger JD; School of Natural Sciences , University of Central Missouri , Warrensburg , Missouri 64093 , United States., Mortenson DE; Department of Chemistry , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States., Huang L; Anatrace , Maumee , Ohio 43537 , United States., Mittal R; Anatrace , Maumee , Ohio 43537 , United States., Travis BR; Anatrace , Maumee , Ohio 43537 , United States., Forest KT; Department of Chemistry , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.; Graduate Program in Biophysics , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.; Department of Bacteriology , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States., Gellman SH; Department of Chemistry , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.; Graduate Program in Biophysics , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States. |
| Abstrakt: |
The structural principles that govern interactions between l- and d-peptides are not well understood. Among natural proteins, coiled-coil assemblies formed between or among α-helices are the most regular feature of tertiary and quaternary structures. We recently reported the first high-resolution structures for heterochiral coiled-coil dimers, which represent a starting point for understanding associations of l- and d-polypeptides. These structures were an unexpected outcome from crystallization of a racemic peptide corresponding to the transmembrane domain of the influenza A M2 protein (M2-TM). The reported structures raised the possibility that heterochiral coiled-coil dimers prefer an 11-residue (hendecad) sequence repeat, in contrast to the 7-residue (heptad) sequence repeat that is dominant among natural coiled coils. To gain insight on sequence repeat preferences of heterochiral coiled-coils, we have examined three M2-TM variants containing substitutions intended to minimize steric clashes between side chains at the coiled-coil interface. In each of the three new crystal structures, we observed heterochiral coiled-coil associations that closely match a hendecad sequence motif, which strengthens the conclusion that this motif is intrinsic to the pairing of α-helices with opposite handedness. In each case, the presence of a hendecad motif was established by comparing the observed helical frequency to that of an ideal hendecad. This comparison revealed that decreasing the size of the amino acid side chain at positions that project toward the superhelical axis produces tighter packing, as determined by the size of the coiled-coil radius. These results provide a basis for future design of heterochiral coiled-coil pairings. |
