PDBsum entry 2knh

Transcription regulator

PDB id: 2knh

Contents

Protein chains

103 a.a. *

18 a.a. *

* Residue conservation analysis

PDB id:

2knh

Name:

Transcription regulator

Title:

The solution structure of the etafh domain of aml1-eto complexed with heb peptide

Structure:

Protein cbfa2t1. Chain: a. Fragment: etafh domain (unp residues 119-216). Synonym: protein mtg8, protein eto, eight twenty one protein, cyclin- d-related protein, zinc finger mynd domain-containing protein 2. Engineered: yes. Transcription factor 12. Chain: b. Fragment: heb peptide (unp residues 11-28).

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: runx1t1, aml1t1, cbfa2t1, cdr, eto, mtg8, zmynd2. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

S.Park,T.Cierpicki,M.Tonelli,J.H.Bushweller

Key ref:

S.Park et al. (2009). Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity. Blood, 113, 3558-3567. PubMed id: 19204326

Date:

25-Aug-09 Release date: 06-Oct-09

Protein chain

Q06455  (MTG8_HUMAN) -  Protein CBFA2T1 from Homo sapiens

Seq: 604 a.a.

Struc: 103 a.a.*

Protein chain

Q99081  (HTF4_HUMAN) -  Transcription factor 12 from Homo sapiens

Seq: 682 a.a.

Struc: 18 a.a.

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

Blood 113:3558-3567 (2009)

PubMed id: 19204326

Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity.

S.Park, W.Chen, T.Cierpicki, M.Tonelli, X.Cai, N.A.Speck, J.H.Bushweller.

ABSTRACT

AML1-ETO is the chimeric protein product of the t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the eTAFH domain, which is homologous to several TATA binding protein-associated factors (TAFs) and interacts with E proteins (E2A and HEB). It has been proposed that AML1-ETO-mediated silencing of E protein function might be important for t(8;21) leukemogenesis. Here, we determined the solution structure of a complex between the AML1-ETO eTAFH domain and an interacting peptide from HEB. On the basis of the structure, key residues in AML1-ETO for HEB association were mutated. These mutations do not impair the ability of AML1-ETO to enhance the clonogenic capacity of primary mouse bone marrow cells and do not eliminate its ability to repress proliferation or granulocyte differentiation. Therefore, the eTAFH-E protein interaction appears to contribute relatively little to the activity of AML1-ETO.