8DJ4

NMR Solution Structure of C-terminally amidated, Full-length Human Galanin

8DJ4 の概要

• エントリーDOI: 10.2210/pdb8dj4/pdb
• 関連するPDBエントリー: 7S3O 7S3Q 7S3R 8DHZ
• NMR情報: BMRB: 31032
• 分子名称: Galanin (1 entity in total)
• 機能のキーワード: synthetic, neuropeptide
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3159.45

構造登録者

Wilkinson, R.E.,Kraichely, K.N.,Buchanan, L.E.,Parnham, S.,Giuliano, M.W. (登録日: 2022-06-30, 公開日: 2022-08-24, 最終更新日: 2024-11-13)

主引用文献

Wilkinson, R.E.,Kraichely, K.N.,Hendy, C.M.,Buchanan, L.E.,Parnham, S.,Giuliano, M.W.
The neuropeptide galanin adopts an irregular secondary structure.
Biochem.Biophys.Res.Commun., 626:121-128, 2022

PubMed Abstract: Human galanin is a 30-residue neuropeptide targeted for development of analgesics, antidepressants, and anticonvulsants. While previous work from our group and others has already produced significant insights into galanin's N-terminal region, no extant structures of galanin in databases include its full-length sequence and the function of its C-terminus remains ambiguous. We report the NMR solution structure of full-length human galanin C-terminal amide, determined from 2D H-H COSY, TOCSY, and ROESY NMR data. Galanin adopts an irregular helical structure across its N-terminus, likely the average of several coiling states. We present the NMR structure of a peptide encompassing the C-terminus of galanin as a stand-alone fragment. The C-terminus of full-length galanin appears to indirectly assist the intramolecular association of hydrophobic sidechains within its N-terminus, remotely rigidifying their position when compared to previously studied N-terminal galanin fragments. By contrast, there is flexibility in the C-terminus of galanin, characterized by two i to i + 2 hydrogen-bonded turns within an otherwise dynamic backbone. The C-terminal portion of the peptide renders it soluble, and plays a hitherto undescribed biophysical role in pre-organizing the galanin receptor binding epitope. We speculate that hydrophilic microdomains of signaling peptides, hormones, and perhaps intrinsically disordered proteins may also function similarly.

PubMed: 35994823
DOI: 10.1016/j.bbrc.2022.08.032

実験手法

SOLUTION NMR