Cryo-electron microscopy of mucins

Mucins, the major polymeric glycoproteins constituting mucus hydrogels, are produced in a complex biosynthetic pathway during which numerous disulfide bonds and glycan modifications are introduced. High-resolution structures have been obtained for over-expressed mucin segments under conditions that mimic the Golgi apparatus, an important station for mucin modification in the secretory pathway. Golgi-like solution conditions promote the self-assembly of the mucin segments into compact, ordered states, which have the dual advantage of illuminating the mechanism for mucin polymerization and being amenable to analysis by single-particle cryo-electron microscopy (cryo-EM). While the structures of these ordered intermediate states may differ from the arrangement and properties of secreted, hydrated, full-length extracellular mucins in gels on epithelial surfaces, they provide insight into the organization of mucin globular domains, and in some cases "disordered" regions, and reveal fundamental aspects of mucin bioassembly. Extending cryo-EM studies to longer mucin fragments and additional mucins may expand our understanding of these remarkable macromolecules.