6TU3

Rat 20S proteasome

6TU3 の概要

• エントリーDOI: 10.2210/pdb6tu3/pdb
• EMDBエントリー: 10586
• 分子名称: Proteasome subunit alpha type-6, Proteasome subunit beta type-3, Proteasome subunit beta type-2, ... (14 entities in total)
• 機能のキーワード: proteasome, hydrolase
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 28
• 化学式量合計: 762568.43

構造登録者

Deshmukh, F.K.,Polkinghorn, C.R.,Elad, N.,Sharon, M. (登録日: 2020-01-02, 公開日: 2020-05-13, 最終更新日: 2024-05-22)

主引用文献

Vimer, S.,Ben-Nissan, G.,Morgenstern, D.,Kumar-Deshmukh, F.,Polkinghorn, C.,Quintyn, R.S.,Vasil'ev, Y.V.,Beckman, J.S.,Elad, N.,Wysocki, V.H.,Sharon, M.
Comparative Structural Analysis of 20S Proteasome Ortholog Protein Complexes by Native Mass Spectrometry.
Acs Cent.Sci., 6:573-588, 2020

PubMed Abstract: Ortholog protein complexes are responsible for equivalent functions in different organisms. However, during evolution, each organism adapts to meet its physiological needs and the environmental challenges imposed by its niche. This selection pressure leads to structural diversity in protein complexes, which are often difficult to specify, especially in the absence of high-resolution structures. Here, we describe a multilevel experimental approach based on native mass spectrometry (MS) tools for elucidating the structural preservation and variations among highly related protein complexes. The 20S proteasome, an essential protein degradation machinery, served as our model system, wherein we examined five complexes isolated from different organisms. We show that throughout evolution, from the archaeal prokaryotic complex to the eukaryotic 20S proteasomes in yeast () and mammals (rat - , rabbit - and human - HEK293 cells), the proteasome increased both in size and stability. Native MS structural signatures of the rat and rabbit 20S proteasomes, which heretofore lacked high-resolution, three-dimensional structures, highly resembled that of the human complex. Using cryoelectron microscopy single-particle analysis, we were able to obtain a high-resolution structure of the rat 20S proteasome, allowing us to validate the MS-based results. Our study also revealed that the yeast complex, and not those in mammals, was the largest in size and displayed the greatest degree of kinetic stability. Moreover, we also identified a new proteoform of the PSMA7 subunit that resides within the rat and rabbit complexes, which to our knowledge have not been previously described. Altogether, our strategy enables elucidation of the unique structural properties of protein complexes that are highly similar to one another, a framework that is valid not only to ortholog protein complexes, but also for other highly related protein assemblies.

PubMed: 32342007
DOI: 10.1021/acscentsci.0c00080

実験手法

ELECTRON MICROSCOPY (2.7 Å)