Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas

Lasse Sprankel; David Vizarraga; Jesús Martín; Sina Manger; Jakob Meier-Credo; Marina Marcos; Noemi Rotllan; Margot P. Scheffer; Joan Carles Escolà-Gil; Julian D. Langer; Jaume Piñol Ribas; Ignacio Fita; Achilleas S. Frangakis

doi:10.1038/s41594-023-00922-y

Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas

Lasse Sprankel, David Vizarraga, Jesús Martín, Sina Manger, Jakob Meier-Credo, Marina Marcos, Noemi Rotllan, Margot P. Scheffer, Joan Carles Escolà-Gil, Julian D. Langer, Jaume Piñol Ribas, Ignacio Fita, Achilleas S. Frangakis

Research output: Contribution to journal › Article › Research › peer-review

4 Citations (Scopus)

Abstract

Mycoplasma pneumoniae, responsible for approximately 30% of community-acquired human pneumonia, needs to extract lipids from the host environment for survival and proliferation. Here, we report a comprehensive structural and functional analysis of the previously uncharacterized protein P116 (MPN_213). Single-particle cryo-electron microscopy of P116 reveals a homodimer presenting a previously unseen fold, forming a huge hydrophobic cavity, which is fully accessible to solvent. Lipidomics analysis shows that P116 specifically extracts lipids such as phosphatidylcholine, sphingomyelin and cholesterol. Structures of different conformational states reveal the mechanism by which lipids are extracted. This finding immediately suggests a way to control Mycoplasma infection by interfering with lipid uptake.

Original language	English
Pages (from-to)	321-329
Number of pages	9
Journal	Nature Structure and Molecular Biology
Volume	30
Issue number	3
DOIs	https://doi.org/10.1038/s41594-023-00922-y
Publication status	Published - 13 Feb 2023

Keywords

Cryoelectron microscopy
Pathogens
Structural biology
Membrane lipids

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Sprankel, L., Vizarraga, D., Martín, J., Manger, S., Meier-Credo, J., Marcos, M., Rotllan, N., Scheffer, M. P., Escolà-Gil, J. C., Langer, J. D., Piñol Ribas, J., Fita, I., & Frangakis, A. S. (2023). Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas. Nature Structure and Molecular Biology, 30(3), 321-329. https://doi.org/10.1038/s41594-023-00922-y

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title = "Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas",

abstract = "Mycoplasma pneumoniae, responsible for approximately 30% of community-acquired human pneumonia, needs to extract lipids from the host environment for survival and proliferation. Here, we report a comprehensive structural and functional analysis of the previously uncharacterized protein P116 (MPN_213). Single-particle cryo-electron microscopy of P116 reveals a homodimer presenting a previously unseen fold, forming a huge hydrophobic cavity, which is fully accessible to solvent. Lipidomics analysis shows that P116 specifically extracts lipids such as phosphatidylcholine, sphingomyelin and cholesterol. Structures of different conformational states reveal the mechanism by which lipids are extracted. This finding immediately suggests a way to control Mycoplasma infection by interfering with lipid uptake.",

keywords = "Cryoelectron microscopy, Pathogens, Structural biology, Membrane lipids",

author = "Lasse Sprankel and David Vizarraga and Jes{\'u}s Mart{\'i}n and Sina Manger and Jakob Meier-Credo and Marina Marcos and Noemi Rotllan and Scheffer, {Margot P.} and Escol{\`a}-Gil, {Joan Carles} and Langer, {Julian D.} and {Pi{\~n}ol Ribas}, Jaume and Ignacio Fita and Frangakis, {Achilleas S.}",

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year = "2023",

month = feb,

day = "13",

doi = "10.1038/s41594-023-00922-y",

language = "English",

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Sprankel, L, Vizarraga, D, Martín, J, Manger, S, Meier-Credo, J, Marcos, M, Rotllan, N, Scheffer, MP, Escolà-Gil, JC, Langer, JD, Piñol Ribas, J, Fita, I & Frangakis, AS 2023, 'Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas', Nature Structure and Molecular Biology, vol. 30, no. 3, pp. 321-329. https://doi.org/10.1038/s41594-023-00922-y

TY - JOUR

T1 - Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas

AU - Sprankel, Lasse

AU - Vizarraga, David

AU - Martín, Jesús

AU - Manger, Sina

AU - Meier-Credo, Jakob

AU - Marcos, Marina

AU - Rotllan, Noemi

AU - Scheffer, Margot P.

AU - Escolà-Gil, Joan Carles

AU - Langer, Julian D.

AU - Piñol Ribas, Jaume

AU - Fita, Ignacio

AU - Frangakis, Achilleas S.

PY - 2023/2/13

Y1 - 2023/2/13

N2 - Mycoplasma pneumoniae, responsible for approximately 30% of community-acquired human pneumonia, needs to extract lipids from the host environment for survival and proliferation. Here, we report a comprehensive structural and functional analysis of the previously uncharacterized protein P116 (MPN_213). Single-particle cryo-electron microscopy of P116 reveals a homodimer presenting a previously unseen fold, forming a huge hydrophobic cavity, which is fully accessible to solvent. Lipidomics analysis shows that P116 specifically extracts lipids such as phosphatidylcholine, sphingomyelin and cholesterol. Structures of different conformational states reveal the mechanism by which lipids are extracted. This finding immediately suggests a way to control Mycoplasma infection by interfering with lipid uptake.

AB - Mycoplasma pneumoniae, responsible for approximately 30% of community-acquired human pneumonia, needs to extract lipids from the host environment for survival and proliferation. Here, we report a comprehensive structural and functional analysis of the previously uncharacterized protein P116 (MPN_213). Single-particle cryo-electron microscopy of P116 reveals a homodimer presenting a previously unseen fold, forming a huge hydrophobic cavity, which is fully accessible to solvent. Lipidomics analysis shows that P116 specifically extracts lipids such as phosphatidylcholine, sphingomyelin and cholesterol. Structures of different conformational states reveal the mechanism by which lipids are extracted. This finding immediately suggests a way to control Mycoplasma infection by interfering with lipid uptake.

KW - Cryoelectron microscopy

KW - Pathogens

KW - Structural biology

KW - Membrane lipids

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U2 - 10.1038/s41594-023-00922-y

DO - 10.1038/s41594-023-00922-y

M3 - Article

C2 - 36782049

SN - 1545-9985

VL - 30

SP - 321

EP - 329

JO - Nature Structure and Molecular Biology

JF - Nature Structure and Molecular Biology

IS - 3

ER -

Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas

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VIRULENCE AND PATHOGENICITY OF MYCOPLASMAS FROM PNEUMONIAE CLUSTER. DESIGN OF ANTIADHESION DRUGS FOR ANTIMICROBIAL THERAPY

Mecanismos de virulencia y regulación en células mínimas: diseño de vacunas contra algunas especies de micoplasmas de interés

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Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas

Abstract

Keywords

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VIRULENCE AND PATHOGENICITY OF MYCOPLASMAS FROM PNEUMONIAE CLUSTER. DESIGN OF ANTIADHESION DRUGS FOR ANTIMICROBIAL THERAPY

Mecanismos de virulencia y regulación en células mínimas: diseño de vacunas contra algunas especies de micoplasmas de interés

Cite this