3D3M

The Crystal Structure of the C-terminal region of Death Associated Protein 5(DAP5)

3D3M の概要

• エントリーDOI: 10.2210/pdb3d3m/pdb
• 分子名称: Eukaryotic translation initiation factor 4 gamma 2 (2 entities in total)
• 機能のキーワード: heat repeat domain, structural genomics, psi, protein structure initiative, israel structural proteomics center, ispc, acetylation, initiation factor, phosphoprotein, protein biosynthesis, repressor, translation regulation, translation
• 由来する生物種: Homo sapiens (man)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39315.13

構造登録者

Dym, O.,Israel Structural Proteomics Center (ISPC) (登録日: 2008-05-12, 公開日: 2008-10-14, 最終更新日: 2024-02-21)

主引用文献

Liberman, N.,Dym, O.,Unger, T.,Albeck, S.,Peleg, Y.,Jacobovitch, Y.,Branzburg, A.,Eisenstein, M.,Marash, L.,Kimchi, A.
The crystal structure of the C-terminal DAP5/p97 domain sheds light on the molecular basis for its processing by caspase cleavage.
J.Mol.Biol., 383:539-548, 2008

PubMed Abstract: DAP5/p97 (death-associated protein 5) is a member of the eukaryotic translation initiation factor 4G family. It functions as a scaffold protein promoting cap-independent translation of proteins. During apoptosis, DAP5/p97 is cleaved by caspases at position 792, yielding an 86-kDa C-terminal truncated isoform (DAP5/p86) that promotes translation of several mRNAs mediated by an internal ribosome entry site. In this study, we report the crystal structure of the C-terminal region of DAP5/p97 extending between amino acids 730 and 897. This structure consists of four HEAT-Repeats and is homologous to the C-terminal domain of eIF4GI, eIF5, and eIF2Bepsilon. Unlike the other proteins, DAP5/p97 lacks electron density in the loop connecting alpha3 and alpha4, which harbors the caspase cleavage site. Moreover, we observe fewer interactions between these two helices. Thus, previous mapping of this site by mutation analysis is confirmed here by the resolved structure of the DAP5/p97 C-terminus. In addition, we identified the position of two conserved aromatic and acidic boxes in the structure of the DAP5/p97 C-terminus. The acidic residues in the two aromatic and acidic boxes form a continuous negatively charged patch, which is suggested to make specific interactions with other proteins such as eIF2beta. The caspase cleavage of DAP5/p97 removes the subdomain carrying acidic residues in the AA-box motif, which may result in exposure of a hydrophobic surface. These intriguing structural differences between the two DAP5 isoforms suggest that they have different interaction partners and, subsequently, different functions.

PubMed: 18722383
DOI: 10.1016/j.jmb.2008.08.013

実験手法

X-RAY DIFFRACTION (1.9 Å)