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J. Biol. Chem., Vol. 282, Issue 23, 16969-16980, June 8, 2007

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Solution Structure of Human Secretory Component and Implications for Biological Function^*

Alexandra Bonner¹, Clémentine Perrier², Blaise Corthésy³, and Stephen J. Perkins⁴

From the Department of Biochemistry and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, United Kingdom and the Service d'Immunologie et d'Allergie, Centre Hospitalier Universitaire Vaudois, BH19-650, Rue du Bugnon, CH-1011 Lausanne, Switzerland

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.

Received for publication, February 12, 2007 , and in revised form, March 9, 2007.

^* The authors have no conflicting financial interests. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The atomic coordinates and structure factors (code 2OCW) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S4.

¹ Supported by the Biotechnology and Biological Sciences Research Council for financial support.

² Supported by a grant from the Nestlé Ph.D. Programme.

³ Supported by the Swiss Science Research Foundation Grant 3200-109545.

⁴ To whom correspondence should be addressed. Tel.: 44-20-7679-7048; Fax: 44-20-7679-7193; E-mail: s.perkins{at}medsch.ucl.ac.uk.

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