Abstract

The cation-π interaction impacts protein folding, structural stability, specificity, and molecular recognition. Cation-π interactions have been overlooked in the lipocalin family. To fill this gap, these interactions were analyzed in the 113 crystal and solution structures from the lipocalin family. The cation-π interactions link previously identified structurally conserved regions and reveal new motifs, which are beyond the reach of a sequence alignment algorithm. Functional and structural significance of the interactions were tested experimentally in human tear lipocalin (TL). TL, a prominent and promiscuous lipocalin, has a key role in lipid binding at the ocular surface. Ligand binding modulation through the loop AB at the "open" end of the barrel has been erroneously attributed solely to electrostatic interactions. Data revealed that the interloop cation-π interaction in the pair Phe28-Lys108 contributes significantly to stabilize the holo-conformation of the loop AB. Numerous energetically significant and conserved cation-π interactions were uncovered in TL and throughout the lipocalin family. Cation-π interactions, such as the highly conserved Trp17-Arg118 pair in TL, were educed in low temperature experiments of mutants with Trp to Tyr substitutions.

Links

Publisher Full Text

Authors

Gasymov OK, Abduragimov AR, Glasgow BJ

Institution

Department of Pathology and Jules Stein Eye Institute, University California at Los Angeles, California 90095, USA. ogassymov@mednet.ucla.edu

Source

Biochemistry 51:14 2012 Apr 10 pg 2991-3002

MeSH

Binding Sites
Cations
Circular Dichroism
Humans
Ligands
Lipocalin 1
Lipocalins
Models, Molecular
Protein Structure, Secondary
Structure-Activity Relationship

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22439821