PDBsum entry 5hiu

Signaling protein

PDB id: 5hiu

Contents

Protein chains

407 a.a.

Waters ×9

PDB id:

5hiu

Name:

Signaling protein

Title:

Structure of the tsc2 n-terminus

Structure:

Gtpase activator-like protein. Chain: a, b, c, d. Synonym: tsc2. Engineered: yes

Source:

Chaetomium thermophilum. Organism_taxid: 209285. Gene: ctht_0061860. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.50Å R-factor: 0.226 R-free: 0.263

Authors:

R.Zech,S.Kiontke,D.Kummel

Key ref:

R.Zech et al. (2016). Structure of the Tuberous Sclerosis Complex 2 (TSC2) N Terminus Provides Insight into Complex Assembly and Tuberous Sclerosis Pathogenesis. J Biol Chem, 291, 20008-20020. PubMed id: 27493206 DOI: 10.1074/jbc.M116.732446

Date:

12-Jan-16 Release date: 10-Aug-16

Protein chains

G0SFF5  (G0SFF5_CHATD) -  GTPase activator-like protein from Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)

Seq: 1734 a.a.

Struc: 407 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M116.732446

J Biol Chem 291:20008-20020 (2016)

PubMed id: 27493206

Structure of the Tuberous Sclerosis Complex 2 (TSC2) N Terminus Provides Insight into Complex Assembly and Tuberous Sclerosis Pathogenesis.

R.Zech, S.Kiontke, U.Mueller, A.Oeckinghaus, D.Kümmel.

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.