6E7K

Structure of the lipoprotein lipase GPIHBP1 complex that mediates plasma triglyceride hydrolysis

Summary for 6E7K

• Entry DOI: 10.2210/pdb6e7k/pdb
• Descriptor: Lipoprotein lipase, Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: hydrolase-cofactor complex, lipid degradation, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 132621.95

Authors

Birrane, G.,Meiyappan, M. (deposition date: 2018-07-26, release date: 2018-12-19, Last modification date: 2024-10-30)

Primary citation

Birrane, G.,Beigneux, A.P.,Dwyer, B.,Strack-Logue, B.,Kristensen, K.K.,Francone, O.L.,Fong, L.G.,Mertens, H.D.T.,Pan, C.Q.,Ploug, M.,Young, S.G.,Meiyappan, M.
Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis.
Proc. Natl. Acad. Sci. U.S.A., 116:1723-1732, 2019

PubMed Abstract: Lipoprotein lipase (LPL) is responsible for the intravascular processing of triglyceride-rich lipoproteins. The LPL within capillaries is bound to GPIHBP1, an endothelial cell protein with a three-fingered LU domain and an N-terminal intrinsically disordered acidic domain. Loss-of-function mutations in or cause severe hypertriglyceridemia (chylomicronemia), but structures for LPL and GPIHBP1 have remained elusive. Inspired by our recent discovery that GPIHBP1's acidic domain preserves LPL structure and activity, we crystallized an LPL-GPIHBP1 complex and solved its structure. GPIHBP1's LU domain binds to LPL's C-terminal domain, largely by hydrophobic interactions. Analysis of electrostatic surfaces revealed that LPL contains a large basic patch spanning its N- and C-terminal domains. GPIHBP1's acidic domain was not defined in the electron density map but was positioned to interact with LPL's large basic patch, providing a likely explanation for how GPIHBP1 stabilizes LPL. The LPL-GPIHBP1 structure provides insights into mutations causing chylomicronemia.

PubMed: 30559189
DOI: 10.1073/pnas.1817984116

Experimental method

X-RAY DIFFRACTION (2.8 Å)