2KYG

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

2KYG の概要

• エントリーDOI: 10.2210/pdb2kyg/pdb
• NMR情報: BMRB: 16954
• 分子名称: cAMP-dependent protein kinase type II-alpha regulatory subunit, Protein CBFA2T1 (2 entities in total)
• 機能のキーワード: protein/protein, homodimer bound to monomer, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 15427.57

構造登録者

Corpora, T.A.,Cierpecki, T.,Bushweller, J. (登録日: 2010-05-25, 公開日: 2010-10-20, 最終更新日: 2024-05-15)

主引用文献

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

実験手法

SOLUTION NMR