Knowledge-based model building of the tertiary structures for lectin domains of the selectin family

A combination of a knowledge-based approach and energy minimization was used to predict the three-dimensional structures of the lectin domains of P-selectin, E-selectin, and L-selectin, respectively. Each of these domains contains 118 amino acids. The starting points for energy minimization were generated based on a framework that consists of a number of separated segments derived from the structure-known carbohydrate-recognition domain of the mannose-binding protein (MBP), which belongs to the same C-type lectin family as the selectin molecules do. The structures thus found for P-, L-, and E-selectin lectin domains share a common feature, i.e., they all contain two alpha-helices, and two antiparallel beta-sheets of which one is formed by two strands (strands 1 and 5) and the other by three (strands 2, 3, and 4). Besides, they all possess two intact disulfide bonds formed by the pair of Cys-19 and Cys-117, and the pair of Cys-90 and Cys-109. The root-mean-square deviations calculated over the set of backbone atoms between P- and L-selectin lectin domains is 3.10 Angstrom, that between P- and E-selectin lectin domains 2.48 Angstrom, and that between L- and E-selectin lectin domains 3.07 Angstrom. A notable feature is the convergence-divergence duality of the 77-107 polypeptide in the three domains; i.e., part of the peptide is folded into a closely similar conformation, and part of it into a highly different one.