Specifying conformational heterogeneity of multi-domain proteins at atomic resolution

被引：3

作者：

Schneider, Tobias ^{[1
,2
]}

Sawade, Kevin ^{[1
,3
]}

Berner, Frederic ^{[1
,2
]}

Peter, Christine ^{[1
,2
]}

Kovermann, Michael ^{[1
,2
]}

机构：

[1] Univ Konstanz, Dept Chem, D-78457 Constance, Germany

[2] Univ Konstanz, Konstanz Res Sch Chem Biol, D-78457 Constance, Germany

[3] Univ Konstanz, Grad Sch Chem, D-78457 Constance, Germany

来源：

STRUCTURE | 2023年 / 31卷 / 10期

关键词：

TRIPLE-RESONANCE EXPERIMENTS; UBIQUITIN CHAINS; DI-UBIQUITIN; STRUCTURAL-ANALYSIS; BACKBONE DYNAMICS; CHEMICAL-SHIFTS; EXCHANGE-RATES; MODEL-FREE; NMR; RELAXATION;

D O I：

10.1016/j.str.2023.07.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The conformational landscape of multi-domain proteins is inherently linked to their specific functions. This also holds for polyubiquitin chains that are assembled by two or more ubiquitin domains connected by a flexible linker thus showing a large interdomain mobility. However, molecular recognition and signal transduction are associated with particular conformational substates that are populated in solution. Here, we apply high -resolu-tion NMR spectroscopy in combination with dual-scale MD simulations to explore the conformational space of K6-, K29-, and K33-linked diubiquitin molecules. The conformational ensembles are evaluated utilizing a para-magnetic cosolute reporting on solvent exposure plus a set of complementary NMR parameters. This approach unravels a conformational heterogeneity of diubiquitins and explains the diversity of structural models that have been determined for K6-, K29-, and K33-linked diubiquitins in free and ligand-bound states so far. We propose a general application of the approach developed here to demystify multi-domain proteins occurring in nature.

引用

页码：1259 / +

页数：27