2NCU
NMR structure of KYE21 in LPS micelles
Summary for 2NCU
| Entry DOI | 10.2210/pdb2ncu/pdb |
| Related | 2NCV 2NCW |
| NMR Information | BMRB: 26036 |
| Descriptor | Heparin cofactor 2 (1 entity in total) |
| Functional Keywords | antimicrobial peptide, antimicrobial protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 2751.28 |
| Authors | Datta, A.,Bhunia, A.,Malmsten, M. (deposition date: 2016-04-18, release date: 2017-03-01, Last modification date: 2024-05-15) |
| Primary citation | Singh, S.,Datta, A.,Schmidtchen, A.,Bhunia, A.,Malmsten, M. Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects. Sci Rep, 7:212-212, 2017 Cited by PubMed Abstract: The objective of the present study is the investigation of possibilities for boosting peptide anti-inflammatory effects by tryptophan end-tagging, including identification of underlying mechanisms for this. In doing so, effects of tryptophan end-tagging of KYE21 (KYEITTIHNLFRKLTHRLFRR), a peptide derived from heparin co-factor II, on membrane and lipopolysaccharide (LPS) interactions were investigated by ellipsometry, NMR, fluorescence spectroscopy, and circular dichroism measurements. Through its N-terminal W stretch, WWWKYE21 displays higher membrane binding, liposome rupture, and bacterial killing than unmodified KYE21. Analogously, W-tagging promotes binding to E. coli LPS and to its endotoxic lipid A moiety. Furthermore, WWWKYE21 causes more stable peptide/LPS complexes than KYE21, as evidenced by detailed NMR studies, adopting a pronounced helical conformation, with a large hydrophobic surface at the N-terminus due to the presence of W-residues, and a flexible C-terminus due to presence of several positively charged arginine residues. Mirroring its increased affinity for LPS and lipid A, WWWKYE21 displays strongly increased anti-inflammatory effect due to a combination of direct lipid A binding, peptide-induced charge reversal of cell membranes for LPS scavenging, and peptide-induced fragmentation of LPS aggregates for improved phagocytosis. Importantly, potent anti-inflammatory effects were observed at low cell toxicity, demonstrated for both monocytes and erythrocytes. PubMed: 28303012DOI: 10.1038/s41598-017-00188-7 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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