Knotted vs. unknotted proteins: evidence of knot-promoting loops.
Knotted proteins, because of their ability to fold reversibly in the same topologically entangled conformation, are the object of an increasing number of experimental and theoretical studies. The aim of the present investigation is to assess, on the basis of presently available structural data, the extent to which knotted proteins are isolated instances in sequence or structure space, and to use comparative schemes to understand whether specific protein segments can be associated to the occurrence of a knot in the native state. A significant sequence homology is found among a sizeable group of knotted and unknotted proteins. In this family, knotted members occupy a primary sub-branch of the phylogenetic tree and differ from unknotted ones only by additional loop segments. These "knot-promoting" loops, whose virtual bridging eliminates the knot, are found in various types of knotted proteins. Valuable insight into how knots form, or are encoded, in proteins could be obtained by targeting these regions in future computational studies or excision experiments.
Potestio
Raffaello
R
SISSA - Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy.
Micheletti
Cristian
C
Orland
Henri
H
D000818:Animals; D024402:Carbonic Anhydrase II / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D007536:Isomerism; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry; D010802:Phylogeny; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000737:chemistry; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D000099253:Trans-Activation Responsive RNA-Binding Protein
D024402:Carbonic Anhydrase II; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C071598:TARBP1 protein, human; D000099253:Trans-Activation Responsive RNA-Binding Protein