6G6J

The crystal structures of Human MYC:MAX bHLHZip complex

6G6J の概要

• エントリーDOI: 10.2210/pdb6g6j/pdb
• 分子名称: Myc proto-oncogene protein, Protein max, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: myc/max, apoptosis
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 43397.06

構造登録者

Allen, M.D.,Zinzalla, G. (登録日: 2018-04-01, 公開日: 2019-04-10, 最終更新日: 2024-02-07)

主引用文献

Sammak, S.,Hamdani, N.,Gorrec, F.,Allen, M.D.,Freund, S.M.V.,Bycroft, M.,Zinzalla, G.
Crystal Structures and Nuclear Magnetic Resonance Studies of the Apo Form of the c-MYC:MAX bHLHZip Complex Reveal a Helical Basic Region in the Absence of DNA.
Biochemistry, 58:3144-3154, 2019

PubMed Abstract: The c-MYC transcription factor is a master regulator of cell growth and proliferation and is an established target for cancer therapy. This basic helix-loop-helix Zip protein forms a heterodimer with its obligatory partner MAX, which binds to DNA via the basic region. Considerable research efforts are focused on targeting the heterodimerization interface and the interaction of the complex with DNA. The only available crystal structure is that of a c-MYC:MAX complex artificially tethered by an engineered disulfide linker and prebound to DNA. We have carried out a detailed structural analysis of the apo form of the c-MYC:MAX complex, with no artificial linker, both in solution using nuclear magnetic resonance (NMR) spectroscopy and by X-ray crystallography. We have obtained crystal structures in three different crystal forms, with resolutions between 1.35 and 2.2 Å, that show extensive helical structure in the basic region. Determination of the α-helical propensity using NMR chemical shift analysis shows that the basic region of c-MYC and, to a lesser extent, that of MAX populate helical conformations. We have also assigned the NMR spectra of the c-MYC basic helix-loop-helix Zip motif in the absence of MAX and showed that the basic region has an intrinsic helical propensity even in the absence of its dimerization partner. The presence of helical structure in the basic regions in the absence of DNA suggests that the molecular recognition occurs via a conformational selection rather than an induced fit. Our work provides both insight into the mechanism of DNA binding and structural information to aid in the development of MYC inhibitors.

PubMed: 31260268
DOI: 10.1021/acs.biochem.9b00296

実験手法

X-RAY DIFFRACTION (2.25 Å)