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首页> 外文期刊>Biochemistry >Photoaffinity Cross-Linking of the Corticotropin-Releasing Factor Receptor Type 1 with Photoreactive Urocortin Analogues
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Photoaffinity Cross-Linking of the Corticotropin-Releasing Factor Receptor Type 1 with Photoreactive Urocortin Analogues

机译：皮质素 - 释放因子受体1型具有光反应性尿道素类似物的交联

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摘要

Interaction of natural peptide ligands with class 2 GPCRs,which are targets of biologically important hormones such as glucagon,secretin,and corticotropin-releasing factor (CRF),occurs with a common orientation,in that the ligand C-terminus binds to the extracellular receptor N-terminus,whereas the ligand N-terminus binds to the receptor juxtamembrane domain.N-Terminal truncation,by eight amino acids in the case of CRF,leads to antagonists,suggesting those residues constitute the receptor activating sequence.Here,we identified by photoaffinity cross-linking using p-benzoyl-L-phenylalanine (Bpa) analogues of urocortin (Ucn) the most affine CRF receptor agonist,interaction domains of CRF_1 receptor with Bpa residues at exclusive positions.Specific cleavage patterns of the corresponding ligand-receptor complexes,obtained using several cleavage methods in combination with SDS-PAGE for fragment size determination,showed that a Bpa group located N-terminally or in position 12 binds at the second and such in position 17 or 22 at the first extracellular receptor loop.Our results indicate that the very N-terminal ligand residues (1 - 11),which are responsible for receptor activation,are oriented to the juxtamembrane domain by interaction of amino acid residues 12,17,and 22.Our findings contradict a recently proposed interaction model derived from ligand interaction with a soluble receptor N-terminus,indicating that conclusions drawn from such a reduced system may be of limited value to understand the interaction with the full-length receptor.
机译：具有2类GPCR的天然肽配体的相互作用，其是生物学上重要激素如胰高血糖素，棘肽和皮质培素释放因子（CRF）的靶标，其与常规取向发生，因为配体C-末端与细胞外受体结合N-末端，而配体N-末端与受体juxtamembrane结构域。在CRF的情况下，在CRF的情况下，通过八个氨基酸，导致拮抗剂，表明这些残基构成受体激活序列。以下，我们识别使用p-benzoyl-l-苯丙氨酸（bpa）的光栅蜜蜂（BPA）的交联尿素素（UCN）是最染色的CRF受体激动剂，CRF_1受体的相互作用域，BPA残基在独占位置。相应配体 - 受体复合物的特异性切割模式，使用几种切割方法与SDS-PAGE结合获得用于片段尺寸测定的，表明位于N-末端或位置12的BPA组在SE结合在第一个细胞外受体回路中的第17或22号处的条件和如22.然后，通过氨基酸的相互作用，对应于受体活化的非常N-末端配体残基（1-11）以氨基酸相互作用取向juxtamembrane结构域4,17和22.our的研究结果将最近提出的与可溶性受体N-末端衍生自配体相互作用的最近提出的相互作用模型，表明从这种减少的系统中抽取的结论可能是有限的，以了解与全部的相互作用有限长度受体。

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  • 来源
    《Biochemistry》 |2005年第47期|共9页
  • 作者

    Oliver Kraetke; Brian Holeran; Hartmut Berger; Emanuel Escher; Michael Bienert; Michael Beyermann;

  • 作者单位

    Department of Peptide Chemistry Institute of Molecular Pharmacology (FMP) 13125 Berlin Germany and Department of Pharmacology Faculty of Medicine Universite de Sherbrooke (IPS) Sherbrooke Quebec Canada J1H 5N4;

    Department of Peptide Chemistry Institute of Molecular Pharmacology (FMP) 13125 Berlin Germany and Department of Pharmacology Faculty of Medicine Universite de Sherbrooke (IPS) Sherbrooke Quebec Canada J1H 5N4;

    Department of Peptide Chemistry Institute of Molecular Pharmacology (FMP) 13125 Berlin Germany and Department of Pharmacology Faculty of Medicine Universite de Sherbrooke (IPS) Sherbrooke Quebec Canada J1H 5N4;

    Department of Peptide Chemistry Institute of Molecular Pharmacology (FMP) 13125 Berlin Germany and Department of Pharmacology Faculty of Medicine Universite de Sherbrooke (IPS) Sherbrooke Quebec Canada J1H 5N4;

    Department of Peptide Chemistry Institute of Molecular Pharmacology (FMP) 13125 Berlin Germany and Department of Pharmacology Faculty of Medicine Universite de Sherbrooke (IPS) Sherbrooke Quebec Canada J1H 5N4;

    Department of Peptide Chemistry Institute of Molecular Pharmacology (FMP) 13125 Berlin Germany and Department of Pharmacology Faculty of Medicine Universite de Sherbrooke (IPS) Sherbrooke Quebec Canada J1H 5N4;

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  • 中图分类 生物化学;
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