Modulation of N- to C-terminal interactions enhances protein stability (1501.02709v1)

Abstract: Although, several factors have been attributed to thermostability, the stabilization strategies used by proteins are still enigmatic. Studies on recombinant xylanase which has the ubiquitous (\b{eta}/{\alpha})8 TIM (Triosephosphate isomerase) barrel fold showed that, just a single extreme N-terminus mutation (V1L) markedly enhanced the thermostability by 5 {\deg}C without loss of catalytic activity whereas another mutation, V1A at the same position decreased the stability by 2 {\deg}C. Based on computational analysis of their crystal structures including residue interaction network, we established a link between N- to C-terminal contacts and protein stability. We demonstrate that augmenting of N- to C-terminal non-covalent interactions is associated with the enhancement of protein stability. We propose that the strategy of mutations at the termini could be exploited with a view to modulate stability without compromising on enzymatic activity, or in general, protein function, in diverse folds where N- and C-termini are in close proximity. Finally, we discuss the implications of our results for the development of therapeutics involving proteins and for designing effective protein engineering strategies.