Structural Basis for TSC-1 TSC-2 Complex Formation
Abstract
Tuberous sclerosis complex (TSC) is a neurological disorder characterized by the formation of hamartomas in brain skin kidney and other organs. The tumor suppressor genes TSCI and TSC2 encode the proteins hamartin and tuberin respectively. The tuberin(1-418) region interacts with hamartin(302-430) forming the TSC1-TSC2 complex that functions in cell growth regulation. Certain mutations in TSC patients disrupt the hamartin-tuberin interaction indicating that association of these proteins is required for their growth suppressing function. However the mechanisms underlying their interaction are poorly understood because their three-dimensional structures are not known. To obtain structural insights into the hamartin-tuberin interaction the hamartin(302-430) and tuberin(11-418) domains were expressed in Escherichia coli cells and purified to homogeneity. Attempts to crystallize the isolated hamartin(302-430) and tuberin(11-418) domains yielded small crystals whereas the hamartin-tuberin heterodimer did not produce crystals. Experiments are in progress to produce diffraction quality crystals of these proteins and determine their structures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2008
- Accession Number
- ADA481926
Entities
People
- John A. Ladias
Organizations
- Beth Israel Deaconess Medical Center