Katarzyna Skorupka,a Seong Kyu Han,b Hyun-Jun Nam,b Sanguk Kimb* and Salem Fahama*
aDepartment of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22093, USA, and bDivision of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Republic of Korea
*Correspondence to : Sanguk Kim, Salem Faham
Domain fusion is a useful tool in protein design. Here, the structure of a fusion of the heterodimeric flagella-assembly proteins FliS and FliC is reported. Although the ability of the fusion protein to maintain the structure of the heterodimer may be apparent, threading-based structural predictions do not properly fuse the heterodimer. Additional examples of naturally occurring heterodimers that are homologous to full-length proteins were identified. These examples highlight that the designed protein was engineered by the same tools as used in the natural evolution of proteins and that heterodimeric structures contain a wealth of information, currently unused, that can improve structural predictions.
Keywords: protein design; protein fusion; protein threading; structure prediction