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

K55I

K55F

K55Y

K55Q

K55E

K55N

SF head group binding to GLTP

“OUT” “IN”

WT D48V

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

HYPOTHESIS

• 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

pGG(CAG)5CC• • • • • • •CC(GAC)5GGp

• • • • • • UC(GUC)5GUUp

pUUG(CUG)5CU

U•UU•U C•CC•CA•AA•A G•GG•G

12

3?

Sequence specific p19?

CNGCNGCNGCNGCNGCNGGNCGNCGNCGNCGNCGNC• • • • • • • • • • • • • • • • • •

2 3

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