PDBsum entry 5hiu

Signaling protein

PDB id: 5hiu

Contents

Protein chains

407 a.a.

Waters ×9

References listed in PDB file

Key reference

• Title: Structure of the tuberous sclerosis complex 2 (tsc2) n terminus provides insight into complex assembly and tuberous sclerosis pathogenesis.
• Authors: R.Zech, S.Kiontke, U.Mueller, A.Oeckinghaus, D.Kümmel.
• Ref.: J Biol Chem, 2016, 291, 20008-20020. [DOI no: 10.1074/jbc.M116.732446]
• PubMed id: 27493206

Note: In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above have been manually determined.

Abstract

Tuberous sclerosis complex (TSC) is caused by mutations in the TSC1 and TSC2 tumor suppressor genes. The gene products hamartin and tuberin form the TSC complex that acts as GTPase-activating protein for Rheb and negatively regulates the mammalian target of rapamycin complex 1 (mTORC1). Tuberin contains a RapGAP homology domain responsible for inactivation of Rheb, but functions of other protein domains remain elusive. Here we show that the TSC2 N terminus interacts with the TSC1 C terminus to mediate complex formation. The structure of the TSC2 N-terminal domain from Chaetomium thermophilum and a homology model of the human tuberin N terminus are presented. We characterize the molecular requirements for TSC1-TSC2 interactions and analyze pathological point mutations in tuberin. Many mutations are structural and produce improperly folded protein, explaining their effect in pathology, but we identify one point mutant that abrogates complex formation without affecting protein structure. We provide the first structural information on TSC2/tuberin with novel insight into the molecular function.

Secondary reference #1

• Title: Structure of the tsc2 n-Terminal domain provides insi into tsc complex assembly and tuberous sclerosis pathogenesis
• Authors: R.Zech, S.Kiontke, U.Mueller, A.Oeckinghaus, D.Kummel.
• Ref.: TO BE PUBLISHED ...