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A lipoprotein lipase (LPL)-specific monoclonal antibody, 88B8, that abolishes the binding of LPL to GPIHBP1

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Christopher M Allan
  • Mikael Larsson
  • Xuchen Hu
  • Cuiwen He
  • Rachel S Jung
  • Alaleh Mapar
  • Constance Voss
  • Kazuya Miyashita
  • Tetsuo Machida
  • Masami Murakami
  • Katsuyuki Nakajima
  • André Bensadoun
  • Ploug, Michael
  • Loren G Fong
  • Stephen G Young
  • Anne P Beigneux

Lipoprotein lipase (LPL) contains two principal domains: an amino-terminal catalytic domain (residues 1-297) and a carboxyl-terminal domain (residues 298-448) that is important for binding lipids and binding GPIHBP1 (an endothelial cell protein that shuttles LPL to the capillary lumen). The LPL sequences required for GPIHBP1 binding have not been examined in detail, but one study suggested that sequences near LPL's carboxyl terminus (residues ~403-438) were crucial. Here, we tested the ability of LPL-specific monoclonal antibodies to block the binding of LPL to GPIHBP1. One antibody, 88B8, abolished LPL binding to GPIHBP1. Consistent with those results, antibody 88B8 could not bind to GPIHBP1-bound LPL on cultured cells. Antibody 88B8 bound poorly to LPL proteins with amino acid substitutions that interfered with GPIHBP1 binding (e.g., C418Y, E421K). However, the sequences near LPL's carboxyl terminus (residues ~403-438) were not sufficient for 88B8 binding; upstream sequences (residues 298-400) were also required. Additional studies showed that these same sequences are required for LPL binding to GPIHBP1. In conclusion, we identified an LPL monoclonal antibody that binds to LPL's GPIHBP1-binding domain. The binding of both antibody 88B8 and GPIHBP1 to LPL depends on large segments of LPL's carboxyl-terminal domain.

OriginalsprogEngelsk
TidsskriftJournal of Lipid Research
Vol/bind57
Udgave nummer10
Sider (fra-til)1889-1898
ISSN0022-2275
DOI
StatusUdgivet - okt. 2016

ID: 166740413