The Analysis of the Human High Affinity IgE Receptor FceRIa from Multiple Crystal Forms

Garman, S C; Sechi, S; Kinet, J -P; Jardetzky, T S

Title: The Analysis of the Human High Affinity IgE Receptor FceRIa from Multiple Crystal Forms

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Abstract

We have solved the structure of the human high affinity IgE receptor, Fc{var_epsilon}RI{alpha}, in six different crystal forms, showing the structure in 15 different chemical environments. This database of structures shows no change in the overall shape of the molecule, as the angle between domains 1 and 2 (D1 and D2) varies little across the ensemble. However, the receptor has local conformational variability in the C' strand of D2 and in the BC loop of D1. In every crystal form, a residue inserts between tryptophan residues 87 and 110, mimicking the position of a proline from the IgE ligand. The different crystal forms reveal a distribution of carbohydrates lining the front and back surfaces of the structure. An analysis of crystal contacts in the different forms indicates regions where the molecule interacts with other proteins, and reveals a potential new binding site distal to the IgE binding site. The results of this study point to new directions for the design of molecules to inhibit the interaction of Fc{var_epsilon}RI{alpha} with its natural ligand and thus to prevent a primary step in the allergic response.

Authors:: Garman, S C; Sechi, S; Kinet, J -P; Jardetzky, T S

Publication Date:: Fri Mar 05 00:00:00 EST 2010

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:: USDOE

OSTI Identifier:: 1006362

Resource Type:: Journal Article

Journal Name:: J. Mol. Biol.

Additional Journal Information:: Journal Volume: 311; Journal Issue: 2001; Journal ID: ISSN 0022-2836

Country of Publication:: United States

Language:: ENGLISH

Subject:: 59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; AFFINITY; CARBOHYDRATES; DESIGN; DISTRIBUTION; LINERS; PROLINE; PROTEINS; RESIDUES; SHAPE; TRYPTOPHAN

Citation Formats


                    Garman, S C, Sechi, S, Kinet, J -P, and Jardetzky, T S. The Analysis of the Human High Affinity IgE Receptor FceRIa from Multiple Crystal Forms.  United States: N. p., 2010. 
        Web.

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                    Garman, S C, Sechi, S, Kinet, J -P, & Jardetzky, T S. The Analysis of the Human High Affinity IgE Receptor FceRIa from Multiple Crystal Forms.  United States.

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                    Garman, S C, Sechi, S, Kinet, J -P, and Jardetzky, T S. 2010.  
        "The Analysis of the Human High Affinity IgE Receptor FceRIa from Multiple Crystal Forms".  United States.

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@article{osti_1006362,

  title        = {The Analysis of the Human High Affinity IgE Receptor FceRIa from Multiple Crystal Forms},

  author       = {Garman, S C and Sechi, S and Kinet, J -P and Jardetzky, T S},

  abstractNote = {We have solved the structure of the human high affinity IgE receptor, Fc{var_epsilon}RI{alpha}, in six different crystal forms, showing the structure in 15 different chemical environments. This database of structures shows no change in the overall shape of the molecule, as the angle between domains 1 and 2 (D1 and D2) varies little across the ensemble. However, the receptor has local conformational variability in the C' strand of D2 and in the BC loop of D1. In every crystal form, a residue inserts between tryptophan residues 87 and 110, mimicking the position of a proline from the IgE ligand. The different crystal forms reveal a distribution of carbohydrates lining the front and back surfaces of the structure. An analysis of crystal contacts in the different forms indicates regions where the molecule interacts with other proteins, and reveals a potential new binding site distal to the IgE binding site. The results of this study point to new directions for the design of molecules to inhibit the interaction of Fc{var_epsilon}RI{alpha} with its natural ligand and thus to prevent a primary step in the allergic response.},

  doi          = {},

  url          = {https://www.osti.gov/biblio/1006362},
  journal      = {J. Mol. Biol.},

  issn         = {0022-2836},

  number       = 2001,

  volume       = 311,

  place        = {United States},

  year         = {Fri Mar 05 00:00:00 EST 2010},

  month        = {Fri Mar 05 00:00:00 EST 2010}

}

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