Fas (CD95, Apo-1, or TNFRSF6) is a prototypical apoptosis-inducing death receptor in the tumor necrosis factor receptor (TNFR) superfamily. While the extracellular domains of TNFRs form trimeric complexes with their ligands and the intracellular domains engage in higher-order oligomerization, the role of the transmembrane (TM) domains is unknown. We determined the NMR structures of mouse and human Fas TM domains in bicelles that mimic lipid bilayers. Surprisingly, these domains use proline motifs to create optimal packing in homotrimer assembly distinct from classical trimeric coiled-coils in solution. Cancer-associated and structure-based mutations in Fas TM disrupt trimerization in vitro and reduce apoptosis induction in vivo, indicating the essential role of intramembrane trimerization in receptor activity. Our data suggest that the structures represent the signaling-active conformation of Fas TM, which appears to be different from the pre-ligand conformation. Analysis of other TNFR sequences suggests proline-containing sequences as common motifs for receptor TM trimerization.
机构:
Univ Chicago, Comm Dev Biol, Chicago, IL 60637 USA
Univ Chicago, Comm Genet, Chicago, IL 60637 USA
Univ Chicago, Comm Canc Biol, Chicago, IL 60637 USA
Univ Chicago, Comm Cell Physiol, Chicago, IL 60637 USA
Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USAUniv Chicago, Comm Dev Biol, Chicago, IL 60637 USA
Seo, Ji-Heui
Suenaga, Atsushi
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机构:
RIKEN Adv Sci Inst, Adv Computat Sci Dept, Computat Syst Biol Res Grp, Kanagawa 2300046, JapanUniv Chicago, Comm Dev Biol, Chicago, IL 60637 USA
Suenaga, Atsushi
Hatakeyama, Mariko
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机构:
RIKEN Adv Sci Inst, Adv Computat Sci Dept, Computat Syst Biol Res Grp, Kanagawa 2300046, JapanUniv Chicago, Comm Dev Biol, Chicago, IL 60637 USA
Hatakeyama, Mariko
Taiji, Makoto
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h-index: 0
机构:
RIKEN Adv Sci Inst, Adv Computat Sci Dept, Computat Syst Biol Res Grp, Kanagawa 2300046, JapanUniv Chicago, Comm Dev Biol, Chicago, IL 60637 USA
机构:
La Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USALa Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
Ying, Ge
Wang, Jing
论文数: 0引用数: 0
h-index: 0
机构:
La Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USALa Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
Wang, Jing
Mallevaey, Thierry
论文数: 0引用数: 0
h-index: 0
机构:
Univ Toronto, Dept Immunol, Toronto, ON M5S 3G9, Canada
Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, CanadaLa Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
Mallevaey, Thierry
Van Calenbergh, Serge
论文数: 0引用数: 0
h-index: 0
机构:
Univ Ghent, Fac Pharmaceut Sci, Lab Med Chem FFW, B-9000 Ghent, BelgiumLa Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
Van Calenbergh, Serge
Zajonc, Dirk M.
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h-index: 0
机构:
La Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
Univ Ghent, Fac Med & Hlth Sci, Dept Internal Med, B-9000 Ghent, BelgiumLa Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
机构:
Super Council Sci Res, Biol Res Ctr, Madrid 28040, SpainNatl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
Klett, Javier
Martin-Santamaria, Sonsoles
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h-index: 0
机构:
Super Council Sci Res, Biol Res Ctr, Madrid 28040, SpainNatl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
Martin-Santamaria, Sonsoles
Gioannini, Theresa L.
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h-index: 0
机构:
Univ Iowa, Dept Microbiol, Carver Coll Med, Inflammat Program, Iowa City, IA 52241 USA
Vet Affairs Med Ctr, Iowa City, IA 52246 USANatl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
Gioannini, Theresa L.
Weiss, Jerrold P.
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h-index: 0
机构:
Univ Iowa, Dept Microbiol, Carver Coll Med, Inflammat Program, Iowa City, IA 52241 USANatl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
Weiss, Jerrold P.
Jerala, Roman
论文数: 0引用数: 0
h-index: 0
机构:
Natl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
Excellent Nucl Magnet Resonance Future Innovat Su, Ljubljana 1000, SloveniaNatl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
机构:
Univ Chicago, Comm Dev Biol, Chicago, IL 60637 USA
Univ Chicago, Comm Genet, Chicago, IL 60637 USA
Univ Chicago, Comm Canc Biol, Chicago, IL 60637 USA
Univ Chicago, Comm Cell Physiol, Chicago, IL 60637 USA
Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USAUniv Chicago, Comm Dev Biol, Chicago, IL 60637 USA
Seo, Ji-Heui
Suenaga, Atsushi
论文数: 0引用数: 0
h-index: 0
机构:
RIKEN Adv Sci Inst, Adv Computat Sci Dept, Computat Syst Biol Res Grp, Kanagawa 2300046, JapanUniv Chicago, Comm Dev Biol, Chicago, IL 60637 USA
Suenaga, Atsushi
Hatakeyama, Mariko
论文数: 0引用数: 0
h-index: 0
机构:
RIKEN Adv Sci Inst, Adv Computat Sci Dept, Computat Syst Biol Res Grp, Kanagawa 2300046, JapanUniv Chicago, Comm Dev Biol, Chicago, IL 60637 USA
Hatakeyama, Mariko
Taiji, Makoto
论文数: 0引用数: 0
h-index: 0
机构:
RIKEN Adv Sci Inst, Adv Computat Sci Dept, Computat Syst Biol Res Grp, Kanagawa 2300046, JapanUniv Chicago, Comm Dev Biol, Chicago, IL 60637 USA
机构:
La Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USALa Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
Ying, Ge
Wang, Jing
论文数: 0引用数: 0
h-index: 0
机构:
La Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USALa Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
Wang, Jing
Mallevaey, Thierry
论文数: 0引用数: 0
h-index: 0
机构:
Univ Toronto, Dept Immunol, Toronto, ON M5S 3G9, Canada
Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, CanadaLa Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
Mallevaey, Thierry
Van Calenbergh, Serge
论文数: 0引用数: 0
h-index: 0
机构:
Univ Ghent, Fac Pharmaceut Sci, Lab Med Chem FFW, B-9000 Ghent, BelgiumLa Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
Van Calenbergh, Serge
Zajonc, Dirk M.
论文数: 0引用数: 0
h-index: 0
机构:
La Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
Univ Ghent, Fac Med & Hlth Sci, Dept Internal Med, B-9000 Ghent, BelgiumLa Jolla Inst Immunol, Div Immune Regulat, La Jolla, CA 92037 USA
机构:
Super Council Sci Res, Biol Res Ctr, Madrid 28040, SpainNatl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
Klett, Javier
Martin-Santamaria, Sonsoles
论文数: 0引用数: 0
h-index: 0
机构:
Super Council Sci Res, Biol Res Ctr, Madrid 28040, SpainNatl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
Martin-Santamaria, Sonsoles
Gioannini, Theresa L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Iowa, Dept Microbiol, Carver Coll Med, Inflammat Program, Iowa City, IA 52241 USA
Vet Affairs Med Ctr, Iowa City, IA 52246 USANatl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
Gioannini, Theresa L.
Weiss, Jerrold P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Iowa, Dept Microbiol, Carver Coll Med, Inflammat Program, Iowa City, IA 52241 USANatl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
Weiss, Jerrold P.
Jerala, Roman
论文数: 0引用数: 0
h-index: 0
机构:
Natl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia
Excellent Nucl Magnet Resonance Future Innovat Su, Ljubljana 1000, SloveniaNatl Inst Chem, Dept Biotechnol, Hajdrihova 19,POB 660, SI-1000 Ljubljana, Slovenia