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Conformational Changes in Mannan-Binding Lectin Bound to Ligand Surfaces¹

Mingdong Dong^2,*,, Sailong Xu^2,*,, Cristiano L. P. Oliveira, Jan S. Pedersen^*,, Steffen Thiel^¶, Flemming Besenbacher^*, and Thomas Vorup-Jensen^3,*,,¶

^* Interdisciplinary Nanoscience Center (iNANO), Department of Physics and Astronomy, Department of Chemistry, and Biophysical Immunology Laboratory, and ^¶ Institute for Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark

The binding of soluble proteins to target surfaces is vital in triggering the immune response. However, structural insight into such processes is still lacking. Mannan-binding lectin (MBL) is a classic example of a pattern recognition molecule with important roles in innate immunity against microbial infections. By small angle x-ray scattering analysis we show that the large MBL complex in solution is folded into a ramified structure with a striking rotational symmetry and a structure permissive of elongation by unbending. Nevertheless, the structure in solution is found to be very stable. However, when the MBL molecule interacts with surface-immobilized ligands, the stable MBL structure is broken into a stretched state with separation of the ligand-binding domains as shown by high resolution atomic force microscopy. These studies provide a snapshot of the single molecule mechanics of MBL and the first direct evidence that the transition from the soluble state to surface-bound protein involves large conformational changes in the quaternary structure, thus highlighting the role of surface topography in immune recognition.

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.

¹ This study was supported by grants from The LEO Pharma Foundation, Danish Medical Research Council, Danish Natural Science Research Foundation, and Danish National Research Foundation.

² These authors contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Thomas Vorup-Jensen, Institute for Medical Microbiology and Immunology, University of Aarhus, Aarhus C, Denmark. E-mail address: vorup-jensen{at}microbiology.au.dk

⁴ Abbreviations used in this paper: MBL, mannan-binding lectin; AFM, atomic force microscopy; CRD, carbohydrate recognition domain; SAXS, small angle x-ray spectroscopy.

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