Abstract
Sphingomyelin and cholesterol are essential lipids that are enriched in plasma membranes of animal cells, where they interact to regulate membrane properties and many intracellular signaling processes. Despite intense study, the interaction between these lipids in membranes is not well understood. Here, structural and biochemical analyses of ostreolysin A (OlyA), a protein that binds to membranes only when they contain both sphingomyelin and cholesterol, reveal that sphingomyelin adopts two distinct conformations in membranes when cholesterol is present. One conformation, bound by OlyA, is induced by stoichiometric, exothermic interactions with cholesterol, properties that are consistent with sphingomyelin/cholesterol complexes. In its second conformation, sphingomyelin is free from cholesterol and does not bind OlyA. A point mutation abolishes OlyA's ability to discriminate between these two conformations. In cells, levels of sphingomyelin/cholesterol complexes are held constant over a wide range of plasma membrane cholesterol concentrations, enabling precise regulation of the chemical activity of cholesterol. The plasma membrane lipid sphingomyelin has two distinct conformations depending on the presence or absence of cholesterol.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1040-1053.e17 |
| Journal | Cell |
| Volume | 176 |
| Issue number | 5 |
| DOIs | |
| State | Published - Feb 21 2019 |
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Keywords
- ALOD4
- cholesterol
- cholesterol homeostasis
- lipid sensors
- ostreolysin A
- plasma membrane structure
- sphingomyelin
- sphingomyelin/cholesterol complexes
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Molecular Discrimination between Two Conformations of Sphingomyelin in Plasma Membranes. / Endapally, Shreya; Frias, Donna; Grzemska, Magdalena; Gay, Austin; Tomchick, Diana R; Radhakrishnan, Arun.
In: Cell, Vol. 176, No. 5, 21.02.2019, p. 1040-1053.e17.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular Discrimination between Two Conformations of Sphingomyelin in Plasma Membranes
AU - Endapally, Shreya
AU - Frias, Donna
AU - Grzemska, Magdalena
AU - Gay, Austin
AU - Tomchick, Diana R
AU - Radhakrishnan, Arun
PY - 2019/2/21
Y1 - 2019/2/21
N2 - Sphingomyelin and cholesterol are essential lipids that are enriched in plasma membranes of animal cells, where they interact to regulate membrane properties and many intracellular signaling processes. Despite intense study, the interaction between these lipids in membranes is not well understood. Here, structural and biochemical analyses of ostreolysin A (OlyA), a protein that binds to membranes only when they contain both sphingomyelin and cholesterol, reveal that sphingomyelin adopts two distinct conformations in membranes when cholesterol is present. One conformation, bound by OlyA, is induced by stoichiometric, exothermic interactions with cholesterol, properties that are consistent with sphingomyelin/cholesterol complexes. In its second conformation, sphingomyelin is free from cholesterol and does not bind OlyA. A point mutation abolishes OlyA's ability to discriminate between these two conformations. In cells, levels of sphingomyelin/cholesterol complexes are held constant over a wide range of plasma membrane cholesterol concentrations, enabling precise regulation of the chemical activity of cholesterol. The plasma membrane lipid sphingomyelin has two distinct conformations depending on the presence or absence of cholesterol.
AB - Sphingomyelin and cholesterol are essential lipids that are enriched in plasma membranes of animal cells, where they interact to regulate membrane properties and many intracellular signaling processes. Despite intense study, the interaction between these lipids in membranes is not well understood. Here, structural and biochemical analyses of ostreolysin A (OlyA), a protein that binds to membranes only when they contain both sphingomyelin and cholesterol, reveal that sphingomyelin adopts two distinct conformations in membranes when cholesterol is present. One conformation, bound by OlyA, is induced by stoichiometric, exothermic interactions with cholesterol, properties that are consistent with sphingomyelin/cholesterol complexes. In its second conformation, sphingomyelin is free from cholesterol and does not bind OlyA. A point mutation abolishes OlyA's ability to discriminate between these two conformations. In cells, levels of sphingomyelin/cholesterol complexes are held constant over a wide range of plasma membrane cholesterol concentrations, enabling precise regulation of the chemical activity of cholesterol. The plasma membrane lipid sphingomyelin has two distinct conformations depending on the presence or absence of cholesterol.
KW - ALOD4
KW - cholesterol
KW - cholesterol homeostasis
KW - lipid sensors
KW - ostreolysin A
KW - plasma membrane structure
KW - sphingomyelin
KW - sphingomyelin/cholesterol complexes
UR - http://www.scopus.com/inward/record.url?scp=85061814815&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061814815&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2018.12.042
DO - 10.1016/j.cell.2018.12.042
M3 - Article
C2 - 30712872
AN - SCOPUS:85061814815
VL - 176
SP - 1040-1053.e17
JO - Cell
JF - Cell
SN - 0092-8674
IS - 5
ER -