Obscurin is a semi-flexible molecule in solution

被引:6
作者
Whitley, Jacob A. [1 ]
Ex-Willey, Aidan M. [1 ,2 ]
Marzolf, Daniel R. [1 ]
Ackermann, Maegen A. [2 ]
Tongen, Anthony L. [3 ]
Kokhan, Oleksandr [1 ]
Wright, Nathan T. [1 ]
机构
[1] James Madison Univ, Dept Chem & Biochem, 901 Carrier Dr,Rm 1174, Harrisonburg, VA 22807 USA
[2] Ohio State Univ, Dept Physiol & Cell Biol, Wexner Med Ctr, Columbus, OH 43210 USA
[3] James Madison Univ, Dept Math & Stat, Harrisonburg, VA 22807 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
obscurin; domai; domain interaction; NMR; SAXS; MD; stretch; M-BAND; BINDING-SITE; TITIN; MUSCLE; NMR; ORGANIZATION; ELASTICITY; MECHANICS; ALIGNMENT; MYOMESIN;
D O I
10.1002/pro.3578
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
Obscurin, a giant modular cytoskeletal protein, is comprised mostly of tandem immunoglobulin-like (Ig-like) domains. This architecture allows obscurin to connect distal targets within the cell. The linkers connecting the Ig domains are usually short (3-4 residues). The physical effect arising from these short linkers is not known; such linkers may lead to a stiff elongated molecule or, conversely, may lead to a more compact and dynamic structure. In an effort to better understand how linkers affect obscurin flexibility, and to better understand the physical underpinnings of this flexibility, here we study the structure and dynamics of four representative sets of dual obscurin Ig domains using experimental and computational techniques. We find in all cases tested that tandem obscurin Ig domains interact at the poles of each domain and tend to stay relatively extended in solution. NMR, SAXS, and MD simulations reveal that while tandem domains are elongated, they also bend and flex significantly. By applying this behavior to a simplified model, it becomes apparent obscurin can link targets more than 200 nm away. However, as targets get further apart, obscurin begins acting as a spring and requires progressively more energy to further elongate.
引用
收藏
页码:717 / 726
页数:10
相关论文
共 50 条
[31]   Revealing the Control Mechanisms of pH on the Solution Properties of Chitin via Single-Molecule Studies [J].
Zhang, Song ;
Yu, Miao ;
Zhang, Guoqiang ;
He, Guanmei ;
Ji, Yunxu ;
Dong, Juan ;
Zheng, Huayan ;
Qian, Lu .
MOLECULES, 2023, 28 (19)
[32]   Aggregation-induced Emission of a Liquid-crystalline Quinolinium Salt Molecule in Aqueous Solution [J].
Tanabe, Kana ;
Kodama, Daisuke ;
Hasegawa, Miki ;
Kato, Takashi .
CHEMISTRY LETTERS, 2014, 43 (02) :184-186
[33]   Morphological Effects on the Small-Molecule-Based Solution-Processed Organic Solar Cells [J].
Lee, Dong-Chan ;
Brownell, Lacie V. ;
Yan, Liang ;
You, Wei .
ACS APPLIED MATERIALS & INTERFACES, 2014, 6 (18) :15767-15773
[34]   Single-molecule Force Spectroscopy of Biomacromolecules Comparative Studies in Aqueous Solution and Nonpolar Solvents [J].
Cui, Shu-xun .
ACTA POLYMERICA SINICA, 2016, (09) :1160-1165
[35]   Semi-analytical solution to plane strain loading of elastic layered coating on an elastic substrate [J].
Vasu, Thamarai Selvan ;
Bhandakkar, Tanmay K. .
SADHANA-ACADEMY PROCEEDINGS IN ENGINEERING SCIENCES, 2015, 40 (07) :2221-2238
[36]   The embryo-specific EMB-1 protein of Daucus carota is flexible and unstructured in solution [J].
Eom, JW ;
Baker, WR ;
Kintanar, A ;
Wurtele, ES .
PLANT SCIENCE, 1996, 115 (01) :17-24
[37]   Modeling of flexible membrane-bound biomolecular complexes for solution small-angle scattering [J].
Barclay, Abigail ;
Kragelund, Birthe B. ;
Arleth, Lise ;
Pedersen, Martin Cramer .
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2023, 635 :611-621
[38]   The importance of suppressing spin diffusion effects in the accurate determination of the spatial structure of a flexible molecule by nuclear Overhauser effect spectroscopy [J].
Khodov, I. A. ;
Efimov, S. V. ;
Klochkov, V. V. ;
Batista de Carvalho, L. A. E. ;
Kiselev, M. G. .
JOURNAL OF MOLECULAR STRUCTURE, 2016, 1106 :373-381
[39]   Elementary processes triggered in curcumin molecule by gas-phase resonance electron attachment and by photoexcitation in solution [J].
Pshenichnyuk, Stanislav A. ;
Asfandiarov, Nail L. ;
Markova, Angelina V. ;
Komolov, Alexei S. ;
Timoshnikov, Viktor A. ;
Polyakov, Nikolay E. .
JOURNAL OF CHEMICAL PHYSICS, 2023, 159 (21)
[40]   Solution structure of a unique C5a semi-synthetic antagonist: Implications in receptor binding [J].
Zhang, XL ;
Boyar, W ;
Galakatos, N ;
Gonnella, NC .
PROTEIN SCIENCE, 1997, 6 (01) :65-72