1A93

NMR SOLUTION STRUCTURE OF THE C-MYC-MAX HETERODIMERIC LEUCINE ZIPPER, NMR, MINIMIZED AVERAGE STRUCTURE

1A93 の概要

• エントリーDOI: 10.2210/pdb1a93/pdb
• NMR情報: BMRB: 4200
• 分子名称: MYC PROTO-ONCOGENE PROTEIN, MAX PROTEIN (2 entities in total)
• 機能のキーワード: leucine zipper, 2d nmr, solution structure, h-bonds, buried salt bridge, proto-oncogene, nuclear protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus, nucleoplasm: P01106; Nucleus: P28574
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7619.71

構造登録者

Lavigne, P.,Crump, M.P.,Gagne, S.M.,Hodges, R.S.,Kay, C.M.,Sykes, B.D. (登録日: 1998-04-15, 公開日: 1998-10-21, 最終更新日: 2024-10-09)

主引用文献

Lavigne, P.,Crump, M.P.,Gagne, S.M.,Hodges, R.S.,Kay, C.M.,Sykes, B.D.
Insights into the mechanism of heterodimerization from the 1H-NMR solution structure of the c-Myc-Max heterodimeric leucine zipper.
J.Mol.Biol., 281:165-181, 1998

PubMed Abstract: The oncoprotein c-Myc (a member of the helix-loop-helix-leucine zipper (b-HLH-LZ) family of transcription factors) must heterodimerize with the b-HLH-LZ Max protein to bind DNA and activate transcription. It has been shown that the LZ domains of the c-Myc and Max proteins specifically form a heterodimeric LZ at 20 degreesC and neutral pH. This suggests that the LZ domains of the c-Myc and Max proteins are playing an important role in the heterodimerization of the corresponding gene products in vivo. Initially, to gain an insight into the energetics of heterodimerization, we studied the stability of N-terminal disulfide-linked versions of the c-Myc and Max homodimeric LZs and c-Myc-Max heterodimeric LZ by fitting the temperature-induced denaturation curves monitored by circular dichroism spectroscopy. The c-Myc LZ does not homodimerize (as previously reported) and the c-Myc-Max heterodimeric LZ is more stable than the Max homodimeric LZ at 20 degreesC and pH 7.0. In order to determine the critical interhelical interactions responsible for the molecular recognition between the c-Myc and Max LZs, the solution structure of the disulfide-linked c-Myc-Max heterodimeric LZ was solved by two-dimensional 1H-NMR techniques at 25 degreesC and pH 4.7. Both LZs are alpha-helical and the tertiary structure depicts the typical left-handed super-helical twist of a two-stranded parallel alpha-helical coiled-coil. A buried salt bridge involving a histidine on the Max LZ and two glutamate residues on the c-Myc LZ is observed at the interface of the heterodimeric LZ. A buried H-bond between an asparagine side-chain and a backbone carbonyl is also observed. Moreover, evidence for e-g interhelical salt bridges is reported. These specific interactions give insights into the preferential heterodimerization process of the two LZs. The low stabilities of the Max homodimeric LZ and the c-Myc-Max heterodimeric LZ as well as the specific interactions observed are discussed with regard to regulation of transcription in this family of transcription factors.

PubMed: 9680483
DOI: 10.1006/jmbi.1998.1914

実験手法

SOLUTION NMR