Structural Insights into Intrinsically Disordered Proteins by Small-Angle X-Ray Scattering

2010 ◽  
pp. 451-476 ◽  
Author(s):  
Pau Bernadó ◽  
Dmitri I. Svergun
Keyword(s):  
Small Angle ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
X Ray ◽  
Intrinsically Disordered ◽  
X Ray Scattering ◽  
Structural Insights ◽  
Ray Scattering

scholarly journals Integrating an Enhanced Sampling Method and Small-Angle X-Ray Scattering to Study Intrinsically Disordered Proteins

2021 ◽  
Vol 8 ◽  
Author(s):  
Chengtao Ding ◽  
Sheng Wang ◽  
Zhiyong Zhang
Keyword(s):  
Experimental Data ◽  
Small Angle ◽  
Sampling Method ◽  
Intrinsically Disordered Proteins ◽  
Md Simulations ◽  
Disordered Proteins ◽  
Enhanced Sampling ◽  
X Ray ◽  
Intrinsically Disordered ◽  
X Ray Scattering

Intrinsically disordered proteins (IDPs) have been paid more and more attention over the past decades because they are involved in a multitude of crucial biological functions. Despite their functional importance, IDPs are generally difficult to investigate because they are very flexible and lack stable structures. Computer simulation may serve as a useful tool in studying IDPs. With the development of computer software and hardware, computational methods, such as molecular dynamics (MD) simulations, are popularly used. However, there is a sampling problem in MD simulations. In this work, this issue is investigated using an IDP called unique long region 11 (UL11), which is the conserved outer tegument component from herpes simplex virus 1. After choosing a proper force field and water model that is suitable for simulating IDPs, integrative modeling by combining an enhanced sampling method and experimental data like small-angle X-ray scattering (SAXS) is utilized to efficiently sample the conformations of UL11. The simulation results are in good agreement with experimental data. This work may provide a general protocol to study structural ensembles of IDPs.

scholarly journals Comment on “Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water”

Science ◽  
2018 ◽  
Vol 361 (6405) ◽  
pp. eaar7101 ◽  
Author(s):  
Robert B. Best ◽  
Wenwei Zheng ◽  
Alessandro Borgia ◽  
Karin Buholzer ◽  
Madeleine B. Borgia ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Small Angle ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Disordered Proteins ◽  
Förster Resonance Energy Transfer ◽  
Unfolded Proteins ◽  
X Ray ◽  
X Ray Scattering ◽  
Ray Scattering

Riback et al. (Reports, 13 October 2017, p. 238) used small-angle x-ray scattering (SAXS) experiments to infer a degree of compaction for unfolded proteins in water versus chemical denaturant that is highly consistent with the results from Förster resonance energy transfer (FRET) experiments. There is thus no “contradiction” between the two methods, nor evidence to support their claim that commonly used FRET fluorophores cause protein compaction.

Structural Insights of the Nucleotide-Dependent Conformational Changes of Thermotoga maritima MutL Using Small-Angle X-ray Scattering Analysis

2008 ◽  
Vol 145 (2) ◽  
pp. 199-206 ◽  
Author(s):  
Tae Gyun Kim ◽  
Hyung Jin Cha ◽  
Hyung Ju Lee ◽  
Seong-Dal Heo ◽  
Kwan Yong Choi ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Small Angle ◽  
Thermotoga Maritima ◽  
X Ray ◽  
X Ray Scattering ◽  
Structural Insights ◽  
Ray Scattering

scholarly journals Architecture and subunit dynamics of the mitochondrial TIM9·10·12 chaperone

2020 ◽  
Author(s):  
Katharina Weinhäupl ◽  
Yong Wang ◽  
Audrey Hessel ◽  
Martha Brennich ◽  
Kresten Lindorff-Larsen ◽  
...  
Keyword(s):  
Md Simulation ◽  
Structural Model ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Free Form ◽  
X Ray ◽  
Intrinsically Disordered ◽  
X Ray Scattering ◽  
Exchange Kinetics ◽  
Binding Groove

The mitochondrial Tim chaperones are responsible for the transport of membrane proteins across the inter-membrane space to the inner and outer mitochondrial membranes. TIM9·10, a hexameric 70 kDa protein complex formed by 3 copies of Tim9 and Tim10, guides its clients across the aqueous compartment. The TIM9·10·12 complex is the anchor point at the inner-membrane insertase complex TIM22. The mechanism of client transport by TIM9·10 has been resolved recently, but the structure and subunit composition of the TIM9·10·12 complex remains largely unresolved. Furthermore, the assembly process of the hexameric TIM chaperones from its subunits remained elusive. We investigate the structural and dynamical properties of the Tim subunits, and show that they are highly dynamic. In their non-assembled form, the subunits behave as intrinsically disordered proteins; when the conserved cysteines of the CX3C-Xn-CX3C motifs are formed, short marginally stable α-helices are formed, which are only fully stabilized upon hexamer formation to the mature chaperone. Subunits are in equilibrium between their hexamer-embedded and a free form, with exchange kinetics on a minutes time scale. Joint NMR, small-angle X-ray scattering and MD simulation data allow us to derive a structural model of the TIM9·10·12 assembly, which has a 2:3:1 stoichiometry (Tim9:Tim10:Tim12) with a conserved hydrophobic client-binding groove and flexible N- and C-terminal tentacles.

scholarly journals Dynamical Oligomerisation of Histidine Rich Intrinsically Disordered Proteins Is Regulated through Zinc-Histidine Interactions

Biomolecules ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 168 ◽  
Author(s):  
Carolina Cragnell ◽  
Lasse Staby ◽  
Samuel Lenton ◽  
Birthe Kragelund ◽  
Marie Skepö
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Intrinsically Disordered Proteins ◽  
Divalent Cations ◽  
Disordered Proteins ◽  
Resonance Spectroscopy ◽  
Binding Motifs ◽  
Histatin 5 ◽  
X Ray ◽  
Intrinsically Disordered ◽  
X Ray Scattering

Intrinsically disordered proteins (IDPs) can form functional oligomers and in some cases, insoluble disease related aggregates. It is therefore vital to understand processes and mechanisms that control pathway distribution. Divalent cations including Zn2+ can initiate IDP oligomerisation through the interaction with histidine residues but the mechanisms of doing so are far from understood. Here we apply a multi-disciplinary approach using small angle X-ray scattering, nuclear magnetic resonance spectroscopy, calorimetry and computations to show that that saliva protein Histatin 5 forms highly dynamic oligomers in the presence of Zn2+. The process is critically dependent upon interaction between Zn2+ ions and distinct histidine rich binding motifs which allows for thermodynamic switching between states. We propose a molecular mechanism of oligomerisation, which may be generally applicable to other histidine rich IDPs. Finally, as Histatin 5 is an important saliva component, we suggest that Zn2+ induced oligomerisation may be crucial for maintaining saliva homeostasis.

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