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In brain, one of the principal GSLs is sulfatide (SF), sulfated derivative of GalCer.
Goals:
• To determine how SO3 group affects SF anchoring to GLTP
• To switch GLTP for SF selectivity
2-
Altered SF level is implicated in Alzheimer’s and
Parkinson’s diseases, multiple sclerosis, progressive
epilepsy with mental retardation and other
neurodegenerative human disorders
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K55I
K55F
K55Y
K55Q
K55E
K55N
SF head group binding to GLTP
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“OUT” “IN”
WT D48V
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PART III. Structural Basis for Suppression of Human Trinucleotide Repeat Expansion Diseases (TREDs)
• repeated CNG-triplet sequences in genes• dynamically unstable, tend to expand• expanded tracts cause many muscle- and
neurodegenerative diseases
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HYPOTHESIS
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• Ye, K., Malinina, L., and Patel, D.J. (2003) Recognition of small interfering RNA by a viral suppressor of RNA silencing. Nature 426, 874-878
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pGG(CAG)5CC• • • • • • •CC(GAC)5GGp
• • • • • • UC(GUC)5GUUp
pUUG(CUG)5CU
U•UU•U C•CC•CA•AA•A G•GG•G
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12
3?
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Sequence specific p19?
CNGCNGCNGCNGCNGCNGGNCGNCGNCGNCGNCGNC• • • • • • • • • • • • • • • • • •
2 3
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Come to Bilbao
Research TeamBorja OchoaBorja Ochoa
Felipe GoñiFelipe Goñi
Sergey IvaninskiySergey Ivaninskiy Aintzane CaboAintzane Cabo
Elizaveta KatorchaElizaveta Katorcha
Sandra DelgadoSandra Delgado Valeria SamyginaValeria Samygina
Jevgenia TamjarJevgenia Tamjar