A tale of two symmetrical tails: Structural and functional characteristics of palindromes in proteins

Abstract

BackgroundIt has been previously shown that palindromic sequences are frequently observed in proteins. However, our knowledge about their evolutionary origin and their possible importance is incomplete.ResultsIn this work, we tried to revisit this relatively neglected phenomenon. Several questions are addressed in this work. (1) It is known that there is a large chance of finding a palindrome in low complexity sequences (i.e. sequences with extreme amino acid usage bias). What is the role of sequence complexity in the evolution of palindromic sequences in proteins? (2) Do palindromes coincide with conserved protein sequences? If yes, what are the functions of these conserved segments? (3) In case of conserved palindromes, is it always the case that the whole conserved pattern is also symmetrical? (4) Do palindromic protein sequences form regular secondary structures? (5) Does sequence similarity of the two "sides" of a palindrome imply structural similarity? For the first question, we showed that the complexity of palindromic peptides is significantly lower than randomly generated palindromes. Therefore, one can say that palindromes occur frequently in low complexity protein segments, without necessarily having a defined function or forming a special structure. Nevertheless, this does not rule out the possibility of finding palindromes which play some roles in protein structure and function. In fact, we found several palindromes that overlap with conserved protein Blocks of different functions. However, in many cases we failed to find any symmetry in the conserved regions of corresponding Blocks. Furthermore, to answer the last two questions, the structural characteristics of palindromes were studied. It is shown that palindromes may have a great propensity to form α-helical structures. Finally, we demonstrated that the two sides of a palindrome generally do not show significant structural similarities.ConclusionWe suggest that the puzzling abundance of palindromic sequences in proteins is mainly due to their frequent concurrence with low-complexity protein regions, rather than a global role in the protein function. In addition, palindromic sequences show a relatively high tendency to form helices, which might play an important role in the evolution of proteins that contain palindromes. Moreover, reverse similarity in peptides does not necessarily imply significant structural similarity. This observation rules out the importance of palindromes for forming symmetrical structures. Although palindromes frequently overlap with conserved Blocks, we suggest that palindromes overlap with Blocks only by coincidence, rather than being involved with a certain structural fold or protein domain.

Unravelling the biodiversity of nanoscale signatures of spider silk fibres

“…Palindromes are a ubiquitous feature of linguistics 43 , music 44 , mathematics 45 , computation 46 and biology 47,48 . The recurrence of palindromes in proteins represents a fundamental paradigm shift in structure-function studies because typical examples exhibit some kind of extraordinary feature 48 or undergo structural distortion under singular conditions 49 . Despite the uncertain contribution of the palindromes to the mechanostructural features observed in the present study, a systematic evaluation of their importance using synthetic biology approaches with recombinant spider silk proteins will be investigated further.…”

KCNA4deficiency leads to a syndrome of abnormal striatum, congenital cataract and intellectual disability

“…The functional role of these segments has not been well understood; it has been speculated that using their ability to expand quickly in time, such abundance may potentiate into increased protein sequence space hence evolving into novel protein functions 39 40. Moreover, a possible role in evolutionary role has also been proposed 41. Considering the main functional domains of the protein, on the other hand, such as Pfam tandem inactivation domain, LCS will have lesser functional properties; hence, dysfunction of two alleles would be required for the gene's deficiency.…”

Uncovering Long Palindromic Sequences in Rice (Oryza sativasubsp.indica) Genome

“…Palindromic sequences have been tied to different genomic rearrangements in different organisms depending on the length of the repeated sequences, although such repeated sequences are usually short and present at several functionally important regions in the genome. However, long palindromic sequences in yeast (Saccharomyces cerevisiae) genome are a major source of genomic instability (Nasar et al 2000;Arunkumar and Nagaraju 2006;Sheari et al 2008). The palindrome-mediated genomic instability is believed to be due to cruciform or hairpin formation and subsequent cleavage of this structure by structure-specific nucleases.…”