Abstract
Lipid rafts have attracted much attention because of their significant functional roles in membrane-associated processes. It is thought that sphingomyelin and cholesterol are essential for forming lipid rafts; however, their motion characteristics are not fully understood despite numerous studies. Here we show accurate local motions encompassing an entire sphingomyelin molecule, which were captured by measuring quadrupole splittings for 19 kinds of site-specifically deuterated sphingomyelins (that is, molecular motion capture of sphingomyelin). The quadrupole splitting profiles, which are distinct from those reported from perdeuterated sphingomyelins or simulation studies, reveal that cholesterol enhances the order in the middle parts of the alkyl chains more efficaciously than at the shallow positions. Comparison with dimyristoylphosphocholine bilayers suggests that cholesterol is deeper in sphingomyelin bilayers, which likely explains the so-called umbrella effect. The experiments also demonstrate that (i) the C2′-C3′ bond predominantly takes the gauche conformation, (ii) the net ordering effect of cholesterol in sphingomyelin bilayers is not larger than that in phosphatidylcholine bilayers, (iii) cholesterol has no specific preference for the acyl or sphingosine chain, (iv) the acyl and sphingosine chains seem mismatched by about two methylene lengths, and (v) the motion of the upper regions of sphingomyelin chains is less temperature dependent than that of lower regions probably due to intermolecular hydrogen bond formation among SM molecules. These insights into the atomic-level dynamics of sphingomyelin provide critical clues to understanding the mechanism of raft formation.
| Original language | English |
|---|---|
| Pages (from-to) | 8363-8370 |
| Number of pages | 8 |
| Journal | Biochemistry |
| Volume | 51 |
| Issue number | 42 |
| DOIs | |
| Publication status | Published - Oct 23 2012 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
Cite this
Comprehensive molecular motion capture for sphingomyelin by site-specific deuterium labeling. / Matsumori, Nobuaki; Yasuda, Tomokazu; Okazaki, Hiroki; Suzuki, Takashi; Yamaguchi, Toshiyuki; Tsuchikawa, Hiroshi; Doi, Mototsugu; Oishi, Tohru; Murata, Michio.
In: Biochemistry, Vol. 51, No. 42, 23.10.2012, p. 8363-8370.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Comprehensive molecular motion capture for sphingomyelin by site-specific deuterium labeling
AU - Matsumori, Nobuaki
AU - Yasuda, Tomokazu
AU - Okazaki, Hiroki
AU - Suzuki, Takashi
AU - Yamaguchi, Toshiyuki
AU - Tsuchikawa, Hiroshi
AU - Doi, Mototsugu
AU - Oishi, Tohru
AU - Murata, Michio
PY - 2012/10/23
Y1 - 2012/10/23
N2 - Lipid rafts have attracted much attention because of their significant functional roles in membrane-associated processes. It is thought that sphingomyelin and cholesterol are essential for forming lipid rafts; however, their motion characteristics are not fully understood despite numerous studies. Here we show accurate local motions encompassing an entire sphingomyelin molecule, which were captured by measuring quadrupole splittings for 19 kinds of site-specifically deuterated sphingomyelins (that is, molecular motion capture of sphingomyelin). The quadrupole splitting profiles, which are distinct from those reported from perdeuterated sphingomyelins or simulation studies, reveal that cholesterol enhances the order in the middle parts of the alkyl chains more efficaciously than at the shallow positions. Comparison with dimyristoylphosphocholine bilayers suggests that cholesterol is deeper in sphingomyelin bilayers, which likely explains the so-called umbrella effect. The experiments also demonstrate that (i) the C2′-C3′ bond predominantly takes the gauche conformation, (ii) the net ordering effect of cholesterol in sphingomyelin bilayers is not larger than that in phosphatidylcholine bilayers, (iii) cholesterol has no specific preference for the acyl or sphingosine chain, (iv) the acyl and sphingosine chains seem mismatched by about two methylene lengths, and (v) the motion of the upper regions of sphingomyelin chains is less temperature dependent than that of lower regions probably due to intermolecular hydrogen bond formation among SM molecules. These insights into the atomic-level dynamics of sphingomyelin provide critical clues to understanding the mechanism of raft formation.
AB - Lipid rafts have attracted much attention because of their significant functional roles in membrane-associated processes. It is thought that sphingomyelin and cholesterol are essential for forming lipid rafts; however, their motion characteristics are not fully understood despite numerous studies. Here we show accurate local motions encompassing an entire sphingomyelin molecule, which were captured by measuring quadrupole splittings for 19 kinds of site-specifically deuterated sphingomyelins (that is, molecular motion capture of sphingomyelin). The quadrupole splitting profiles, which are distinct from those reported from perdeuterated sphingomyelins or simulation studies, reveal that cholesterol enhances the order in the middle parts of the alkyl chains more efficaciously than at the shallow positions. Comparison with dimyristoylphosphocholine bilayers suggests that cholesterol is deeper in sphingomyelin bilayers, which likely explains the so-called umbrella effect. The experiments also demonstrate that (i) the C2′-C3′ bond predominantly takes the gauche conformation, (ii) the net ordering effect of cholesterol in sphingomyelin bilayers is not larger than that in phosphatidylcholine bilayers, (iii) cholesterol has no specific preference for the acyl or sphingosine chain, (iv) the acyl and sphingosine chains seem mismatched by about two methylene lengths, and (v) the motion of the upper regions of sphingomyelin chains is less temperature dependent than that of lower regions probably due to intermolecular hydrogen bond formation among SM molecules. These insights into the atomic-level dynamics of sphingomyelin provide critical clues to understanding the mechanism of raft formation.
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UR - http://www.scopus.com/inward/citedby.url?scp=84867801841&partnerID=8YFLogxK
U2 - 10.1021/bi3009399
DO - 10.1021/bi3009399
M3 - Article
C2 - 23016915
AN - SCOPUS:84867801841
VL - 51
SP - 8363
EP - 8370
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 42
ER -