6wt3

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

spinqualitylabelsall models 6wt3, resolution 2.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6wt3 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.85Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 alpha-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the alpha-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL. The structural basis for monoclonal antibody 5D2 binding to the tryptophan-rich loop of lipoprotein lipase.,Luz JG, Beigneux AP, Asamoto DK, He C, Song W, Allan CM, Morales J, Tu Y, Kwok A, Cottle T, Meiyappan M, Fong LG, Kim JE, Ploug M, Young SG, Birrane G J Lipid Res. 2020 Oct;61(10):1347-1359. doi: 10.1194/jlr.RA120000993. Epub 2020 , Jul 20. PMID:32690595 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA