title: Biophysical and Biochemical Characterization of Avian Secretory Component Provides Structural Insights into the Evolution of the Polymeric Ig Receptor.
abstract: The polymeric Ig receptor (pIgR) transports polymeric Abs across epithelia to the mucosa, where proteolytic cleavage releases the ectodomain (secretory component [SC]) as an integral component of secretory Abs, or as an unliganded protein that can mediate interactions with bacteria. SC is conserved among vertebrates, but domain organization is variable: mammalian SC has five domains (D1-D5), whereas avian, amphibian, and reptilian SC lack the D2 domain, and fish SC lacks domains D2-D4. In this study, we used double electron-electron resonance spectroscopy and surface plasmon resonance binding studies to characterize the structure, dynamics, and ligand binding properties of avian SC, avian SC domain variants, and a human SC (hSC) variant lacking the D2 domain. These experiments demonstrated that, unlike hSC, which adopts a compact or "closed" domain arrangement, unliganded avian SC is flexible and exists in both closed and open states, suggesting that the mammalian SC D2 domain stabilizes the closed conformation observed for hSC D1-D5. Experiments also demonstrated that avian and mammalian pIgR share related, but distinct, mechanisms of ligand binding. Together, our data reveal differences in the molecular recognition mechanisms associated with evolutionary changes in the pIgR protein.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125;
authors.forename: Beth M
authors.identifier: 0000-0003-0637-3206
authors.initials: BM
authors.lastname: Stadtmueller
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095; and Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Zhongyu
authors.identifier: 0000-0002-3018-3608
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125;
authors.forename: Kathryn E
authors.identifier: 0000-0002-4683-8138
authors.initials: KE
authors.lastname: Huey-Tubman
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125;
authors.forename: Helena
authors.initials: H
authors.lastname: Roberts-Mataric
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095; and Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Hubbell
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125; bjorkman@caltech.edu.
authors.forename: Pamela J
authors.identifier: 0000-0002-2277-3990
authors.initials: PJ
authors.lastname: Bjorkman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D002850:Chromatography, Gel; D019143:Evolution, Molecular; D006801:Humans; D000072417:Protein Domains; D019056:Receptors, Polymeric Immunoglobulin / Q000737:chemistry*; D012635:Secretory Component / Q000737:chemistry*; D016415:Sequence Alignment; D020349:Surface Plasmon Resonance
chemical_list: D019056:Receptors, Polymeric Immunoglobulin; D012635:Secretory Component