The role of Gc protein oligosaccharide structure as a risk factor for COPD

The risk of chronic obstructive pulmonary disease (COPD) is related to Gc protein allele type, such as Gc*1F, Gc*IS, Gc*2. It has been reported that Gc*1F increased COPD risk, while Gc*2 suppressed the risk. Thus, the allele type of Gc protein is an important factor in COPD. These Gc proteins differ in sugar composition at Thr418 or Thr420. In this study, features of the sugar structure of modeled Gc proteins were investigated.

Gc protein (GclF, Gc1S, Gc2) models were constructed based on X-ray data of vitamin D binding protein (ID=1J7E) using InsightII-Discover with the Homology module, and the molecular orbital (MO) parameters [e.g., dipole moment, solvation free energy (dGW)] of the oligosaccharide were analyzed.

The MO parameter of the sugar moiety was different for each Gc protein model. In beta-1,4 bond models, the dipole moment of Gc2 protein was larger (56.6 debye) than Gcl type (GclF: 21.9, Gc1S: 29.8 debye) protein, and it was directed towards the intermolecular space. The Gc2 oligosaccharide region was the most hydrophobic (dGW=-999.4 KI) among the Gc proteins analyzed in this study. The electrostatic potential (ESP) field of beta-1,4 type Gc2 protein was similarly distributed to beta-1,4 linked Gcl-type proteins (GclF, GclS). In the beta-1,3 type Gc protein models, the results of these parameters (i.e., dipole moment, dGW and ESP) were similar to those of beta-1,4 type models.

The relationship between COPD risk and the features of the sugar structure in Gc proteins was examined, and it appeared that the active factors (i.e., dipole moment, dGW) might be risk factors for COPD, but passive factors (i.e., ESP) did not affect COPD risk. The bond type (beta-1,4 or beta-1,3) between galactose and N-acetylgalactosamine did not affect the molecular features.