2RME

Stressin

2RME の概要

• エントリーDOI: 10.2210/pdb2rme/pdb
• 関連するPDBエントリー: 2RMI 2rm9 2rmd 2rmf 2rmg 2rmh
• 分子名称: Stressin (1 entity in total)
• 機能のキーワード: crf ligand, sauvagine, astressin2b, urocortins, urotensins, crf receptors, neuropeptide
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4456.21

構造登録者

Grace, C.R.R.,Perrin, M.H.,Cantle, J.P.,Vale, W.W.,Rivier, J.E.,Riek, R. (登録日: 2007-10-16, 公開日: 2008-01-01, 最終更新日: 2024-10-30)

主引用文献

Grace, C.R.R.,Perrin, M.H.,Cantle, J.P.,Vale, W.W.,Rivier, J.E.,Riek, R.
Common and divergent structural features of a series of corticotropin releasing factor-related peptides
J.Am.Chem.Soc., 129:16102-16114, 2007

PubMed Abstract: Members of the corticoliberin family include the corticotropin releasing factors (CRFs), sauvagine, the urotensins, and urocortin 1 (Ucn1), which bind to both the CRF receptors CRF-R1 and CRF-R2, and the urocortins 2 (Ucn2) and 3 (Ucn3), which are selective agonists of CRF-R2. Structure activity relationship studies led to several potent and long-acting analogues with selective binding to either one of the receptors. NMR structures of six ligands of this family (the antagonists astressin B and astressin2-B, the agonists stressin1, and the natural ligands human Ucn1, Ucn2, and Ucn3) were determined in DMSO. These six peptides show differences in binding affinities, receptor-selectivity, and NMR structure. Overall, their backbones are alpha-helical, with a small kink or a turn around residues 25-27, resulting in a helix-loop-helix motif. The C-terminal helices are of amphipathic nature, whereas the N-terminal helices vary in their amphipathicity. The C-terminal helices thereby assume a conformation very similar to that of astressin bound to the ECD1 of CRF-R2 recently reported by our group.1 On the basis of an analysis of the observed 3D structures and relative potencies of [Ala]-substituted analogues, it is proposed that both helices could play a crucial role in receptor binding and selectivity. In conclusion, the C-terminal helices may interact along their hydrophobic faces with the ECD1, whereas the entire N-terminal helical surface may be involved in receptor activation. On the basis of the common and divergent features observed in the 3D structures of these ligands, multiple binding models are proposed that may explain their plurality of actions.

PubMed: 18052377
DOI: 10.1021/ja0760933

実験手法

SOLUTION NMR