2KNH

The Solution structure of the eTAFH domain of AML1-ETO complexed with HEB peptide

Summary for 2KNH

• Entry DOI: 10.2210/pdb2knh/pdb
• NMR Information: BMRB: 16467
• Descriptor: Protein CBFA2T1, Transcription factor 12 (2 entities in total)
• Functional Keywords: aml1-eto, etafh, heb, dna-binding, metal-binding, nucleus, proto-oncogene, transcription, transcription regulation, zinc-finger, developmental protein, phosphoprotein, transcription regulator
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 13613.66

Authors

Park, S.,Cierpicki, T.,Tonelli, M.,Bushweller, J.H. (deposition date: 2009-08-25, release date: 2009-10-06, Last modification date: 2024-05-01)

Primary citation

Park, S.,Chen, W.,Cierpicki, T.,Tonelli, M.,Cai, X.,Speck, N.A.,Bushweller, J.H.
Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity.
Blood, 113:3558-3567, 2009

PubMed 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.

PubMed: 19204326
DOI: 10.1182/blood-2008-06-161307

Experimental method

SOLUTION NMR