PDBsum entry: 2d5r

Transcription

PDB id: 2d5r

Contents

Protein chains

252 a.a. *

116 a.a. *

Waters ×90

* Residue conservation analysis

PDB id:

2d5r

Name:

Transcription

Title:

Crystal structure of a tob-hcaf1 complex

Structure:

Ccr4-not transcription complex subunit 7. Chain: a. Fragment: poly(a) deadenylase. Synonym: ccr4-associated factor 1, caf1, btg1 binding factor 1. Engineered: yes. Tob1 protein. Chain: b. Fragment: btg/tob domain.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.50Å R-factor: 0.223 R-free: 0.246

Authors:

M.Horiuchi,N.N.Suzuki,N.Muroya,K.Takahasi,M.Nishida, Y.Yoshida,N.Ikematsu,T.Nakamura,J.Kawamura-Tsuzuku, T.Yamamoto,F.Inagaki

Key ref:

M.Horiuchi et al. (2009). Structural Basis for the Antiproliferative Activity of the Tob-hCaf1 Complex. J Biol Chem, 284, 13244-13255. PubMed id: 19276069 DOI: 10.1074/jbc.M809250200

Date:

04-Nov-05 Release date: 12-Dec-06

Protein chain

Q9UIV1  (CNOT7_HUMAN) -  CCR4-NOT transcription complex subunit 7

Seq: 285 a.a.

Struc: 252 a.a.

Protein chain

P50616  (TOB1_HUMAN) -  Protein Tob1

Seq: 345 a.a.

Struc: 116 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (1 term)
• Biochemical function: nucleic acid binding (1 term)

DOI no: 10.1074/jbc.M809250200

J Biol Chem 284:13244-13255 (2009)

PubMed id: 19276069

Structural Basis for the Antiproliferative Activity of the Tob-hCaf1 Complex.

M.Horiuchi, K.Takeuchi, N.Noda, N.Muroya, T.Suzuki, T.Nakamura, J.Kawamura-Tsuzuku, K.Takahasi, T.Yamamoto, F.Inagaki.

ABSTRACT

The Tob/BTG family is a group of antiproliferative proteins containing two highly homologous regions, Box A and Box B. These proteins all associate with CCR4-associated factor 1 (Caf1), which belongs to the ribonuclease D (RNase D) family of deadenylases and is a component of the CCR4-Not deadenylase complex. Here we determined the crystal structure of the complex of the N-terminal region of Tob and human Caf1 (hCaf1). Tob exhibited a novel fold, whereas hCaf1 most closely resembled the catalytic domain of yeast Pop2 and human poly(A)-specific ribonuclease. Interestingly, the association of hCaf1 was mediated by both Box A and Box B of Tob. Cell growth assays using both wild-type and mutant proteins revealed that deadenylase activity of Caf1 is not critical but complex formation is crucial to cell growth inhibition. Caf1 tethers Tob to the CCR4-Not deadenylase complex, and thereby Tob gathers several factors at its C-terminal region, such as poly(A)-binding proteins, to exert antiproliferative activity.

Selected figure(s)

Figure 1.
Structure of the TobN138-hCaf1 complex. A, ribbon diagram of the TobN138-hCaf1 complex labeled with secondary structures. hCaf1 is shown in light yellow and TobN138 in gray. Box A and Box B of Tob are shown in red and blue, respectively. The F[o] - F[c]omit map of the interacting residues of Trp-93t and Lys-203t at 1.0 σ contour level is displayed in the right panel. B, the side chains of the active site residues, enclosed by a circle, are shown as ball-and-stick models. C, the electrostatic surface potential of the hCaf1-TobN138 complex calculated by GROMACS. The view shown is from the same orientation as in B. Figs. 1, 4, and 5 were prepared with PyMOL.

Figure 5.
Biologically significant motifs in Tob. A, interaction sites of TobN138 with hCaf1. The residues that mediate the association of TobN138 with hCaf1 are shown as a stick model on the ribbon diagram. Water molecules are indicated by green dots. Box A and Box B regions of TobN138 are colored red and blue, respectively. B, Erk binding sites on Tob. The Arg residues binding to Erk are indicated as a stick model and colored purple. The Lys residues identified as the nuclear localization signal are also indicated as a stick model and colored purple. C, putative nuclear export signal (NES82-92) on Tob. The putative nuclear export signal, LX[(1-3)]LX[(2-3)]LXL, is indicated in yellow. The side chains of NES82-92 are shown as a stick model.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 13244-13255) copyright 2009.

Figures were selected by the author.