8DHZ
NMR Structure of Ac-hGal(17-30)NH2, an N-terminally acetylated fragment of the C-terminus of human galanin
Summary for 8DHZ
| Entry DOI | 10.2210/pdb8dhz/pdb |
| Related | 7S3O 7S3Q 7S3R 8DJ4 |
| NMR Information | BMRB: 31029 |
| Descriptor | Galanin (1 entity in total) |
| Functional Keywords | fragment, neuropeptide |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 1546.65 |
| Authors | Kraichely, K.N.,Hendy, C.M.,Parnham, S.,Giuliano, M.W. (deposition date: 2022-06-28, release date: 2022-08-24, Last modification date: 2024-10-23) |
| Primary citation | 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 Cited by 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: 35994823DOI: 10.1016/j.bbrc.2022.08.032 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
