5Z5X

HVF18 in complex with LPS micelles

5Z5X の概要

• エントリーDOI: 10.2210/pdb5z5x/pdb
• 分子名称: Peptide from Prothrombin (1 entity in total)
• 機能のキーワード: thrombin c-terminal peptide, synthetic peptide, lps binding peptide, antimicrobial protein
• 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: 2276.70

構造登録者

Saravanan, R.,Schmidtchen, A. (登録日: 2018-01-21, 公開日: 2018-03-07, 最終更新日: 2024-05-01)

主引用文献

Saravanan, R.,Holdbrook, D.A.,Petrlova, J.,Singh, S.,Berglund, N.A.,Choong, Y.K.,Kjellstrom, S.,Bond, P.J.,Malmsten, M.,Schmidtchen, A.
Structural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides.
Nat Commun, 9:2762-2762, 2018

PubMed Abstract: Thrombin-derived C-terminal peptides (TCPs) of about 2 kDa are present in wounds, where they exert anti-endotoxic functions. Employing a combination of nuclear magnetic resonance spectroscopy (NMR), biophysical, mass spectrometry and cellular studies combined with in silico multiscale modelling, we here determine the bound conformation of HVF18 (HVFRLKKWIQKVIDQFGE), a TCP generated by neutrophil elastase, in complex with bacterial lipopolysaccharide (LPS) and define a previously undisclosed interaction between TCPs and human CD14. Further, we show that TCPs bind to the LPS-binding hydrophobic pocket of CD14 and identify the peptide region crucial for TCP interaction with LPS and CD14. Taken together, our results demonstrate the role of structural transitions in LPS complex formation and CD14 interaction, providing a molecular explanation for the previously observed therapeutic effects of TCPs in experimental models of bacterial sepsis and endotoxin shock.

PubMed: 30018388
DOI: 10.1038/s41467-018-05242-0

実験手法

SOLUTION NMR