6WT3

Structural basis for the binding of monoclonal antibody 5D2 to the tryptophan-rich lipid-binding loop in lipoprotein lipase

6WT3 の概要

• エントリーDOI: 10.2210/pdb6wt3/pdb
• 関連するPDBエントリー: 6WN4
• 分子名称: 5D2 FAB HEAVY CHAIN, 5D2 FAB LIGHT CHAIN (3 entities in total)
• 機能のキーワード: 5d2, lipoprotein lipase, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47780.11

構造登録者

Luz, J.G.,Birrane, G.,Young, S.G.,Meiyappan, M.,Ploug, M. (登録日: 2020-05-01, 公開日: 2020-07-29, 最終更新日: 2024-10-16)

主引用文献

Luz, J.G.,Beigneux, A.P.,Asamoto, D.K.,He, C.,Song, W.,Allan, C.M.,Morales, J.,Tu, Y.,Kwok, A.,Cottle, T.,Meiyappan, M.,Fong, L.G.,Kim, J.E.,Ploug, M.,Young, S.G.,Birrane, G.
The structural basis for monoclonal antibody 5D2 binding to the tryptophan-rich loop of lipoprotein lipase.
J.Lipid Res., 61:1347-1359, 2020

PubMed Abstract: For three decades, the LPL-specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that 5D2 binds with high affinity to a synthetic LPL peptide containing the Trp-rich loop of human (but not mouse) LPL. We also showed, by both fluorescence and UV resonance Raman spectroscopy, that the Trp-rich loop binds lipids. Finally, we used X-ray crystallography to solve the structure of the Trp-rich peptide bound to a 5D2 Fab fragment. The Trp-rich peptide contains a short α-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the α-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL.

PubMed: 32690595
DOI: 10.1194/jlr.RA120000993

実験手法

X-RAY DIFFRACTION (2.85 Å)