The crystal structure of the major cat allergen Fel d 1, a member of the secretoglobin family

被引:99
作者
Kaiser, L
Grönlund, H
Sandalova, T
Ljunggren, HG
van Hage-Hamsten, M
Achour, A
Schneider, G
机构
[1] Huddinge Univ Hosp, Karolinska Inst, Dept Med, Ctr Infect Med, S-14186 Huddinge, Sweden
[2] Karolinska Inst & Hosp L2 04, Dept Med, Unit Clin Immunol & Allergy, S-17176 Stockholm, Sweden
[3] Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden
关键词
D O I
10.1074/jbc.M304740200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The domestic cat (Felis domesticus) is one of the most important causes of allergic asthma worldwide. The dominating cat allergen, Fel d 1, is composed of two heterodimers. Recently, it has been shown that recombinant Fel d 1, consisting of chain 2 and chain 1 fused together without additional linker, has immunological properties indistinguishable from the natural heterodimeric protein. Herein, we report the crystal structure of recombinant monomeric Fel d 1 at 1.85-Angstrom resolution, determined by multi-wavelength anomalous diffraction using selenomethionine substituted protein. Fel d 1 is an all-helical protein and consists of eight helices. The two halves of the recombinant Fel d 1 molecule, corresponding to the wild-type Fel d 1 chains, are very similar in three-dimensional structure, despite the lack of significant sequence identity. The structure of the Fel d 1 presents a striking similarity to that of uteroglobin, a steroid-inducible cytokine-like molecule with anti-inflammatory and immunomodulatory properties. An internal, asymmetric cavity is formed in the Fel d 1 that could bind an endogenous ligand. The distribution of residues lining this cavity suggests that such a ligand must be amphipathic. The structure of Fel d 1 displays the localization of three previously defined Fel d 1 IgE epitopes on the surface of the protein. The three-dimensional structure provides a framework for rational design of hypoallergenic mutants aimed for treatment of cat allergy.
引用
收藏
页码:37730 / 37735
页数:6
相关论文
共 55 条
[1]  
Aalberse RC, 2000, J ALLERGY CLIN IMMUN, V106, P228, DOI 10.1067/mai.2000.108434
[2]   Worsening of asthma in children allergic to cats, after indirect exposure to cat at school [J].
Almqvist, C ;
Wickman, M ;
Perfetti, L ;
Berglind, N ;
Renström, A ;
Hedrén, M ;
Larsson, K ;
Hedlin, G ;
Malmberg, P .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2001, 163 (03) :694-698
[3]   A COMPARATIVE-STUDY OF THE ALLERGENS OF CAT URINE, SERUM, SALIVA, AND PELT [J].
ANDERSON, MC ;
BAER, H ;
OHMAN, JL .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1985, 76 (04) :563-569
[4]   THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].
BAILEY, S .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763
[5]   STRUCTURE AND REFINEMENT OF THE OXIDIZED P21 FORM OF UTEROGLOBIN AT 1.64 A RESOLUTION [J].
BALLY, R ;
DELETTRE, J .
JOURNAL OF MOLECULAR BIOLOGY, 1989, 206 (01) :153-170
[6]   WHERE DOES CAT ALLERGEN-1 COME FROM [J].
BARTHOLOME, K ;
KISSLER, W ;
BAER, H ;
KOPIETZSCHULTE, E ;
WAHN, U .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1985, 76 (03) :503-506
[7]   NATIVE AND RECOMBINANT FEL-DI AS PROBES INTO THE RELATIONSHIP OF ALLERGEN STRUCTURE TO HUMAN IGE IMMUNOREACTIVITY [J].
BOND, JF ;
BRAUER, AW ;
SEGAL, DB ;
NAULT, AK ;
ROGERS, BL ;
KUO, MC .
MOLECULAR IMMUNOLOGY, 1993, 30 (16) :1529-1541
[8]   Allergen immunotherapy: Therapeutic vaccines for allergic diseases - A WHO position paper [J].
Bousquet, J ;
Lockey, R ;
Malling, HJ .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1998, 102 (04) :558-562
[9]   Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].
Brunger, AT ;
Adams, PD ;
Clore, GM ;
DeLano, WL ;
Gros, P ;
Grosse-Kunstleve, RW ;
Jiang, JS ;
Kuszewski, J ;
Nilges, M ;
Pannu, NS ;
Read, RJ ;
Rice, LM ;
Simonson, T ;
Warren, GL .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921
[10]   USE OF MOLECULAR REPLACEMENT IN THE STRUCTURE DETERMINATION OF THE P21212 AND THE P21 (PSEUDO P21212) CRYSTAL FORMS OF OXIDIZED UTEROGLOBIN [J].
BUEHNER, M ;
LIFCHITZ, A ;
BALLY, R ;
MORNON, JP .
JOURNAL OF MOLECULAR BIOLOGY, 1982, 159 (02) :353-358