Abstract
Among several ‘anion binding motifs’, the recently described ‘CαNN’ motif occurring in the loop regions preceding a helix, is conserved through evolution both in sequence and its conformation. To establish the significance of the conserved sequence and their intrinsic affinity for anions, a series of peptides containing the naturally occurring ‘CαNN’ motif at the N-terminus of a designed helix, have been modeled and studied in a context free system using computational techniques. Appearance of a single interacting site with negative binding free-energy for both the sulfate and phosphate ions, as evidenced in docking experiments, establishes that the ‘CαNN’ segment has an intrinsic affinity for anions. Molecular Dynamics (MD) simulation studies reveal that interaction with anion triggers a conformational switch from non-helical to helical state at the ‘CαNN’ segment, which extends the length of the anchoring-helix by one turn at the N-terminus. Computational experiments substantiate the significance of sequence/structural context and justify the conserved nature of the ‘CαNN’ sequence for anion recognition through “local” interaction.
Highlights
Proteins, the ubiquitous biopolymers, in several occasions interact with anions through non-covalent interactions which modulate and stabilize their 3D-structures
The binding free energy and the interaction parameters obtained from the computational study suggest that the anion recognition/binding is thermodynamically favorable; it depends on the conformation of the motif segment and the nature of the interacting anion
The helical conformation induced at this four-residue segment of the ‘CaNN’ anion-binding motif upon anion binding may occur as a result of the co-operative effect initiated during the approach of anion towards the ‘motif’ segment and be augmented by the anchoring helix which may have an implication for nucleation of folding
Summary
The ubiquitous biopolymers, in several occasions interact with anions through non-covalent interactions which modulate and stabilize their 3D-structures. ‘CaNN’ [13], ‘nests’ [14,15,16], ‘structural P-loop’ [17], ‘cup’ [18] along with motifs for recognizing adenine, adenine-containing nucleotides and its analogues [12,19,20]], the recently identified ‘CaNN’ motif [13], common to more than 100 fold-representative protein structures as observed in the FSSP database, has a specially characteristic feature This motif consists of main chain atoms of three consecutive residues (Ca21N0, N+1), often present in the active sites of proteins and participates directly in several key regulating functions [1,2,3,21]. This motif, usually possessing a spatial geometry of a right-handed baa or bab backbone conformation, upon interaction with anion endures an accompanying conformational change from a non-helical to a helical state at the ‘CaNN’ segment that extends the length of the anchoring-helix by one turn towards its N-terminus
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