2KYG

Structure of the AML1-ETO Nervy Domain - PKA(RIIa) complex and its contribution to AML1-ETO activity

Summary for 2KYG

• Entry DOI: 10.2210/pdb2kyg/pdb
• NMR Information: BMRB: 16954
• Descriptor: cAMP-dependent protein kinase type II-alpha regulatory subunit, Protein CBFA2T1 (2 entities in total)
• Functional Keywords: protein/protein, homodimer bound to monomer, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 15427.57

Authors

Corpora, T.A.,Cierpecki, T.,Bushweller, J. (deposition date: 2010-05-25, release date: 2010-10-20, Last modification date: 2024-05-15)

Primary citation

Corpora, T.,Roudaia, L.,Oo, Z.M.,Chen, W.,Manuylova, E.,Cai, X.,Chen, M.J.,Cierpicki, T.,Speck, N.A.,Bushweller, J.H.
Structure of the AML1-ETO NHR3-PKA(RIIalpha) complex and its contribution to AML1-ETO activity.
J.Mol.Biol., 402:560-577, 2010

PubMed Abstract: AML1-ETO is the chimeric protein product of t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the nervy homology region (NHR) 3 domain, which shares homology with A-kinase anchoring proteins and interacts with the regulatory subunit of type II cAMP-dependent protein kinase A (PKA(RIIα)). We determined the solution structure of a complex between the AML1-ETO NHR3 domain and PKA(RIIα). Based on this structure, a key residue in AML1-ETO for PKA(RIIα) association was mutated. This mutation did not disrupt AML1-ETO's ability to enhance the clonogenic capacity of primary mouse bone marrow cells or its ability to repress proliferation or granulocyte differentiation. Introduction of the mutation into AML1-ETO had minimal impact on in vivo leukemogenesis. Therefore, the NHR3-PKA(RIIα) protein interaction does not appear to significantly contribute to AML1-ETO's ability to induce leukemia.

PubMed: 20708017
DOI: 10.1016/j.jmb.2010.08.007

Experimental method

SOLUTION NMR