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Publication Abstract from PubMed

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 (1)H-(1)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.

The neuropeptide galanin adopts an irregular secondary structure.,Wilkinson RE, Kraichely KN, Hendy CM, Buchanan LE, Parnham S, Giuliano MW Biochem Biophys Res Commun. 2022 Oct 20;626:121-128. doi: , 10.1016/j.bbrc.2022.08.032. Epub 2022 Aug 15. PMID:35994823^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.