4kk1
Crystal Structure of TSC1 core domain from S. pombe
Structural highlights
FunctionTSC1_SCHPO Together with tsc2, required for uptake of various amino-acids from the environment and for proper conjugation. Involved in induction of gene expression of permeases and genes required for meiosis upon nitrogen starvation. May act as a GTPase-activating protein (GAP) for the small GTPase rhb1.[1] [2] [3] Publication Abstract from PubMedTuberous sclerosis complex is a disease caused by mutations in two tumor-suppressor genes, TSC1 and TSC2. The TSC1 protein, also known as hamartin, has a critical role in controlling mTOR signalling. TSC1 does not bear apparent sequence homology with other proteins. Here we show that the N-terminal half of yeast TSC1 forms a protease-resistant domain, which is evolutionarily conserved. The crystal structure of this yeast TSC1 core domain shows that it contains a pseudo-HEAT repeat fold with its C-terminal end capped by a helical subdomain. This allows us to model the three-dimensional structure of the human TSC1 N-terminal domain (TSC1-NTD), which anchors essentially all pathogenic TSC1 missense mutations found in tuberous sclerosis patients. Interestingly, most pathogenic mutations map inside of the folded TSC1-NTD structure, whereas most non-pathogenic variants are on the structural surface. This indicates that the disruption of the TSC1-NTD globular structure is a major cause of tuberous sclerosis. Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations.,Sun W, Zhu YJ, Wang Z, Zhong Q, Gao F, Lou J, Gong W, Xu W Nat Commun. 2013 Jul 16;4:2135. doi: 10.1038/ncomms3135. PMID:23857276[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
