title: Solution structure of human secretory component and implications for biological function.
abstract: Secretory component (SC) in association with polymeric IgA (pIgA) forms secretory IgA, the major antibody active at mucosal surfaces. SC also exists in the free form, with innate-like neutralizing properties against pathogens. Free SC consists of five glycosylated variable (V)-type Ig domains (D1-D5), whose structure was determined by x-ray and neutron scattering, ultracentrifugation, and modeling. With a radius of gyration of 3.53-3.63 nm, a length of 12.5 nm, and a sedimentation coefficient of 4.0 S, SC possesses an unexpected compact structure. Constrained scattering modeling based on up to 13,000 trial models shows that SC adopts a J-shaped structure in which D4 and D5 are folded back against D2 and D3. The seven glycosylation sites are located on one side of SC, leaving known IgA-binding motifs free to interact with pIgA. This work represents the first analysis of the three-dimensional structure of full-length free SC and paves the way to a better understanding of the association between SC and its potential ligands, i.e. pIgA and pathogenic-associated motifs.
authors.affiliation: Department of Biochemistry and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bonner
authors.forename: Clémentine
authors.initials: C
authors.lastname: Perrier
authors.forename: Blaise
authors.initials: B
authors.lastname: Corthésy
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Perkins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012542:Scattering, Radiation; D012635:Secretory Component / Q000737:chemistry* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D014461:Ultracentrifugation
chemical_list: D012635:Secretory Component; D012996:Solutions