SASDDM9: lipoprotein lipase–GPIHBP1 complex (Lipoprotein lipase, hLPL + Gl...

Basic information

• Entry: Database: SASBDB / ID: SASDDM9

Sample

lipoprotein lipase–GPIHBP1 complex

• Lipoprotein lipase (protein), hLPL, Homo sapiens
• Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (protein), GPIHBP1, Homo sapiens

Function / homology

Function:

lipoprotein lipase / low-density lipoprotein particle mediated signaling / chylomicron remodeling / lipoprotein lipase activity / positive regulation of cholesterol storage / phospholipase A1 / phospholipase activity / phospholipase A1 activity / Assembly of active LPL and LIPC lipase complexes / triglyceride catabolic process / very-low-density lipoprotein particle remodeling / Chylomicron remodeling / positive regulation of lipid storage / chylomicron / cellular response to nutrient / high-density lipoprotein particle remodeling / triacylglycerol lipase activity / very-low-density lipoprotein particle / heparan sulfate proteoglycan binding / positive regulation of macrophage derived foam cell differentiation / triglyceride homeostasis / positive regulation of chemokine (C-X-C motif) ligand 2 production / carboxylic ester hydrolase activity / cellular response to fatty acid / triglyceride metabolic process / lipoprotein particle binding / apolipoprotein binding / catalytic complex / positive regulation of fat cell differentiation / retinoid metabolic process / response to glucose / Retinoid metabolism and transport / positive regulation of chemokine production / protein-membrane adaptor activity / phospholipid metabolic process / positive regulation of adipose tissue development / cholesterol homeostasis / positive regulation of interleukin-1 beta production / fatty acid metabolic process / response to bacterium / Transcriptional regulation of white adipocyte differentiation / positive regulation of interleukin-6 production / positive regulation of inflammatory response / fatty acid biosynthetic process / positive regulation of tumor necrosis factor production / heparin binding / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / signaling receptor binding / calcium ion binding / cell surface / protein homodimerization activity / extracellular space / extracellular region / plasma membrane

Domain/homology:

Lipoprotein lipase / Lipase, LIPH-type / Lipase, N-terminal / Triacylglycerol lipase family / Lipase / Lipase / Lipoxygenase homology 2 (beta barrel) domain / PLAT/LH2 domain / PLAT/LH2 domain superfamily / PLAT/LH2 domain / PLAT domain profile. / Lipases, serine active site. / Alpha/Beta hydrolase fold

Component:

Lipoprotein lipase

• Biological species: Homo sapiens (human)
• Citation: Journal: Proc Natl Acad Sci U S A / Year: 2019; Title: Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis.; Authors: Gabriel Birrane / Anne P Beigneux / Brian Dwyer / Bettina Strack-Logue / Kristian Kølby Kristensen / Omar L Francone / Loren G Fong / Haydyn D T Mertens / Clark Q Pan / Michael Ploug / Stephen G Young / Muthuraman Meiyappan / ; 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.

Contact author

• Haydyn Mertens (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

Models

• Model #2159: ; Type: dummy / Software: (2.8.1) / Radius of dummy atoms: 2.20 A / Symmetry: P2 / Chi-square value: 1.067 / P-value: 0.382446; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: lipoprotein lipase–GPIHBP1 complex / Specimen concentration: 0.72 mg/ml / Entity id: 1184 / 1185
• Buffer: Name: 10 mM BisTris, 150 mM NaCl, 4 mM CaCl2, 10% glycerol / pH: 7.4

Entity #1184

Name: hLPL / Type: protein / Description: Lipoprotein lipase / Formula weight: 50.323 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P06858
Sequence:

DQRRDFIDIE SKFALRTPED TAEDTCHLIP GVAESVATCH FNHSSKTFMV IHGWTVTGMY ESWVPKLVAA LYKREPDSNV IVVDWLSRAQ EHYPVSAGYT KLVGQDVARF INWMEEEFNY PLDNVHLLGY SLGAHAAGIA GSLTNKKVNR ITGLDPAGPN FEYAEAPSRL SPDDADFVDV LHTFTRGSPG RSIGIQKPVG HVDIYPNGGT FQPGCNIGEA IRVIAERGLG DVDQLVKCSH ERSIHLFIDS LLNEENPSKA YRCSSKEAFE KGLCLSCRKN RCNNLGYEIN KVRAKRSSKM YLKTRSQMPY KVFHYQVKIH FSGTESETHT NQAFEISLYG TVAESENIPF TLPEVSTNKT YSFLIYTEVD IGELLMLKLK WKSDSYFSWS DWWSSPGFAI QKIRVKAGET QKKVIFCSRE KVSHLQKGKA PAVFVKCHDK SLNKKSG

Entity #1185

Name: GPIHBP1 / Type: protein
Description: Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
Formula weight: 14.713 / Num. of mol.: 2 / Source: Homo sapiens
Sequence:

QTQQEEEEED EDHGPDDYDE EDEDEVEEEE TNRLPGGRSR VLLRCYTCKS LPRDERCNLT QNCSHGQTCT TLIAHGNTES GLLTTHSTWC TDSCQPITKT VEGTQVTMTC CQSSLCNVPP WQSSRVQDPT G

Experimental information

• Beam: Instrument name: PETRA III EMBL P12 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotron / Wavelength: 0.124 Å / Dist. spec. to detc.: 3.1 mm
• Detector: Name: Pilatus 2M

Scan

Title: lipoprotein lipase–GPIHBP1 complex / Measurement date: Dec 2, 2017 / Storage temperature: 25 °C / Cell temperature: 25 °C / Exposure time: 0.05 sec. / Number of frames: 20 / Unit: 1/nm /

	Min	Max
Q	0.0918	5.0879

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 787 /

	Min	Max
Q	0.0586472	2.23301
P(R) point	1	787
R	0	19

Result

Type of curve: single_conc

	Experimental	Standard	Standard error	Porod
MW	152 kDa	151.9 kDa	10	188 kDa
Volume	-	-	-	319 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	0.07501	0.01	0.074	0.01
Radius of gyration, Rg	5.598 nm	0.01	5.47 nm	0.01

	Min	Max	Error
D	-	19	5
Guinier point	1	55	-