PDBsum entry 2ypb

Immune system

PDB id: 2ypb

Contents

Protein chains

67 a.a.

74 a.a.

DNA/RNA

PDB id:

2ypb

Name:

Immune system

Title:

Structure of the scl:e47 complex bound to DNA

Structure:

T-cell acute lymphocytic leukemia protein 1. Chain: a. Fragment: bhlh, residues 5-78. Synonym: tal-1, class a basic helix-loop-helix protein 17, bhlha17, stem cell protein, t-cell leukemia/lymphoma protein 5, scl. Engineered: yes. Transcription factor e2-alpha. Chain: b. Fragment: residues 535-613.

Source:

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

Resolution:

2.87Å R-factor: 0.255 R-free: 0.288

Authors:

K.El Omari,S.J.Hoosdally,K.Tuladhar,D.Karia,E.Ponsele,O.Platonova, P.Vyas,R.Patient,C.Porcher,E.J.Mancini

Key ref:

K.El Omari et al. (2013). Structural basis for LMO2-driven recruitment of the SCL:E47bHLH heterodimer to hematopoietic-specific transcriptional targets. Cell Rep, 4, 135-147. PubMed id: 23831025 DOI: 10.1016/j.celrep.2013.06.008

Date:

30-Oct-12 Release date: 31-Jul-13

Protein chain

P17542  (TAL1_HUMAN) -  T-cell acute lymphocytic leukemia protein 1 from Homo sapiens

Seq: 331 a.a.

Struc: 67 a.a.

Protein chain

P15923  (TFE2_HUMAN) -  Transcription factor E2-alpha from Homo sapiens

Seq: 654 a.a.

Struc: 74 a.a.*

* PDB and UniProt seqs differ at 17 residue positions (black crosses)

DNA/RNA chains

A-C-C-A-T-C-T-G-T-T-C 11 bases

G-A-A-C-A-G-A-T-G-G-T 11 bases

DOI no: 10.1016/j.celrep.2013.06.008

Cell Rep 4:135-147 (2013)

PubMed id: 23831025

Structural basis for LMO2-driven recruitment of the SCL:E47bHLH heterodimer to hematopoietic-specific transcriptional targets.

K.El Omari, S.J.Hoosdally, K.Tuladhar, D.Karia, E.Hall-Ponselé, O.Platonova, P.Vyas, R.Patient, C.Porcher, E.J.Mancini.

ABSTRACT

Cell fate is governed by combinatorial actions of transcriptional regulators assembling into multiprotein complexes. However, the molecular details of how these complexes form are poorly understood. One such complex, which contains the basic-helix-loop-helix heterodimer SCL:E47 and bridging proteins LMO2:LDB1, critically regulates hematopoiesis and induces T cell leukemia. Here, we report the crystal structure of (SCL:E47)bHLH:LMO2:LDB1LID bound to DNA, providing a molecular account of the network of interactions assembling this complex. This reveals an unexpected role for LMO2. Upon binding to SCL, LMO2 induces new hydrogen bonds in SCL:E47, thereby strengthening heterodimer formation. This imposes a rotation movement onto E47 that weakens the heterodimer:DNA interaction, shifting the main DNA-binding activity onto additional protein partners. Along with biochemical analyses, this illustrates, at an atomic level, how hematopoietic-specific SCL sequesters ubiquitous E47 and associated cofactors and supports SCL's reported DNA-binding-independent functions. Importantly, this work will drive the design of small molecules inhibiting leukemogenic processes.