© 2005 The Japanese Biochemical Society
Regular Paper |
NMR Study on the Major Mite Allergen Der f 2: Its Refined Tertiary Structure, Epitopes for Monoclonal Antibodies and Characteristics Shared by ML Protein Group Members
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1 Department of Material and Biological Sciences, Faculty of Science, Japan Women’s University, Mejirodai, Bunkyo-ku, Tokyo 112-8681; 2 The Department of Molecular Physiology, Tokyo Metropolitan Institute of Medical Sciences, Honkomagome, Bunkyo-ku, Tokyo 113-8613; and 3 Bioscience Research and Development Laboratory, Asahi Breweries, Ltd., 1-1-21, Midori, Moriya, Ibaraki 302-0106
To whom correspondence should be addressed at the present address. Tel: +81-92-642-6969, Fax: +81-92-642-6764, E-mail: hideki{at}sls.kyushu-u.ac.jp
ABSTRACT
Group 2 major mite allergens Der f 2 and Der p 2 are classified into the recently identified group of MD-2-related lipid-recognition (ML) proteins, but the ligands and biological functions of these allergens are unknown. We have obtained a high-quality NMR structure for Der f 2, and found that it is more similar to the crystal structure of NPC2, a distant homologue, than to that of Der p 2, in terms of the separation and angle between the two major ß-sheets. This made us propose that ML proteins undergo clamshell-like motions that change the sizes of ligand-binding spaces inside their immunoglobulin-fold ß-sandwich to accommodate lipid molecules. This type of motion in lipopolysaccaride recognition of MD-2 is suggested to be likely as well by structural models. We also report the applicability of NMR differential exchange broadening experiments for complexes of intact monoclonal antibodies and antigens; using this technique, we have detected the conformational epitopes for monoclonal antibodies 15E11 and 13A4 as two separate surface patches.
FOOTNOTES
* Present address: Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421.
Present address: Division of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812.
Present address: Graduate School of Systems Life Sciences, Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581.
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