Glycosylation modulates melanoma cell ?2?1 and ?3?1 integrin interactions with type IV collagen.

ABSTRACT: Although type IV collagen is heavily glycosylated, the influence of this post-translational modification on integrin binding has not been investigated. In the present study, galactosylated and nongalactosylated triple-helical peptides have been constructed containing the ?1(IV)382-393 and ?1(IV)531-543 sequences, which are binding sites for the ?2?1 and ?3?1 integrins, respectively. All peptides had triple-helical stabilities of 37 °C or greater. The galactosylation of Hyl(393) in ?1(IV)382-393 and Hyl(540) and Hyl(543) in ?1(IV)531-543 had a dose-dependent influence on melanoma cell adhesion that was much more pronounced in the case of ?3?1 integrin binding. Molecular modeling indicated that galactosylation occurred on the periphery of ?2?1 integrin interaction with ?1(IV)382-393 but right in the middle of ?3?1 integrin interaction with ?1(IV)531-543. The possibility of extracellular deglycosylation of type IV collagen was investigated, but no ?-galactosidase-like activity capable of collagen modification was found. Thus, glycosylation of collagen can modulate integrin binding, and levels of glycosylation could be altered by reduction in expression of glycosylation enzymes but most likely not by extracellular deglycosylation activity.

SUBMITTER: Stawikowski MJ 

PROVIDER: S-EPMC4118119 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature