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

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Standard

Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis. / Birrane, Gabriel; Beigneux, Anne P; Dwyer, Brian; Strack-Logue, Bettina; Kristensen, Kristian Kølby; Francone, Omar L; Fong, Loren G; Mertens, Haydyn D T; Pan, Clark Q; Ploug, Michael; Young, Stephen G; Meiyappan, Muthuraman.

I: Proceedings of the National Academy of Sciences of the United States of America, Bind 116, Nr. 5, 2019, s. 1723-1732.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Birrane, G, Beigneux, AP, Dwyer, B, Strack-Logue, B, Kristensen, KK, Francone, OL, Fong, LG, Mertens, HDT, Pan, CQ, Ploug, M, Young, SG & Meiyappan, M 2019, 'Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis', Proceedings of the National Academy of Sciences of the United States of America, bind 116, nr. 5, s. 1723-1732. https://doi.org/10.1073/pnas.1817984116

APA

Birrane, G., Beigneux, A. P., Dwyer, B., Strack-Logue, B., Kristensen, K. K., Francone, O. L., ... Meiyappan, M. (2019). Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis. Proceedings of the National Academy of Sciences of the United States of America, 116(5), 1723-1732. https://doi.org/10.1073/pnas.1817984116

Vancouver

Birrane G, Beigneux AP, Dwyer B, Strack-Logue B, Kristensen KK, Francone OL o.a. Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis. Proceedings of the National Academy of Sciences of the United States of America. 2019;116(5):1723-1732. https://doi.org/10.1073/pnas.1817984116

Author

Birrane, Gabriel ; Beigneux, Anne P ; Dwyer, Brian ; Strack-Logue, Bettina ; Kristensen, Kristian Kølby ; Francone, Omar L ; Fong, Loren G ; Mertens, Haydyn D T ; Pan, Clark Q ; Ploug, Michael ; Young, Stephen G ; Meiyappan, Muthuraman. / Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis. I: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Bind 116, Nr. 5. s. 1723-1732.

Bibtex

@article{b8edd608316d45dea8f151fc6e7acd5d,
title = "Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis",
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 LPL or GPIHBP1 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.",
keywords = "Animals, CHO Cells, Capillaries/metabolism, Cell Line, Cricetulus, Crystallography, X-Ray/methods, Endothelial Cells/metabolism, Humans, Hydrolysis, Hypertriglyceridemia/metabolism, Lipoprotein Lipase/metabolism, Plasma/metabolism, Receptors, Lipoprotein/metabolism, Triglycerides/blood",
author = "Gabriel Birrane and Beigneux, {Anne P} and Brian Dwyer and Bettina Strack-Logue and Kristensen, {Kristian K{\o}lby} and Francone, {Omar L} and Fong, {Loren G} and Mertens, {Haydyn D T} and Pan, {Clark Q} and Michael Ploug and Young, {Stephen G} and Muthuraman Meiyappan",
note = "Copyright {\circledC} 2019 the Author(s). Published by PNAS.",
year = "2019",
doi = "10.1073/pnas.1817984116",
language = "English",
volume = "116",
pages = "1723--1732",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "5",

}

RIS

TY - JOUR

T1 - Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis

AU - Birrane, Gabriel

AU - Beigneux, Anne P

AU - Dwyer, Brian

AU - Strack-Logue, Bettina

AU - Kristensen, Kristian Kølby

AU - Francone, Omar L

AU - Fong, Loren G

AU - Mertens, Haydyn D T

AU - Pan, Clark Q

AU - Ploug, Michael

AU - Young, Stephen G

AU - Meiyappan, Muthuraman

N1 - Copyright © 2019 the Author(s). Published by PNAS.

PY - 2019

Y1 - 2019

N2 - 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 LPL or GPIHBP1 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.

AB - 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 LPL or GPIHBP1 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.

KW - Animals

KW - CHO Cells

KW - Capillaries/metabolism

KW - Cell Line

KW - Cricetulus

KW - Crystallography, X-Ray/methods

KW - Endothelial Cells/metabolism

KW - Humans

KW - Hydrolysis

KW - Hypertriglyceridemia/metabolism

KW - Lipoprotein Lipase/metabolism

KW - Plasma/metabolism

KW - Receptors, Lipoprotein/metabolism

KW - Triglycerides/blood

U2 - 10.1073/pnas.1817984116

DO - 10.1073/pnas.1817984116

M3 - Journal article

C2 - 30559189

VL - 116

SP - 1723

EP - 1732

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 5

ER -

ID: 216914567