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
[21]   Investigations on a flexible prolyl-endopeptidase inhibitor in solution by NMR techniques [J].
Podányi, B ;
Bokotey, S ;
Kánai, K ;
Fehér, M ;
Hermecz, I .
MAGNETIC RESONANCE IN CHEMISTRY, 1999, 37 (05) :346-352
[22]   A Flexible Solution to Anion Transport: Powerful Anionophores Based on a Cyclohexane Scaffold [J].
Cooper, James A. ;
Street, Steven T. G. ;
Davis, Anthony P. .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2014, 53 (22) :5609-5613
[23]   Single Molecule Discrimination of Heteropolytungstates and Their Isomers in Solution with a Nanometer-Scale Pore [J].
Ettedgui, Jessica ;
Kasianowicz, John J. ;
Balijepalli, Arvind .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2016, 138 (23) :7228-7231
[25]   Hierarchically structured self-supported latex films for flexible and semi-transparent electronics [J].
Maattanen, Anni ;
Ihalainen, Petri ;
Torngren, Bjorn ;
Rosqvist, Emil ;
Pesonen, Markus ;
Peltonen, Jouko .
APPLIED SURFACE SCIENCE, 2016, 364 :37-44
[26]   Flexible actuator by electric bending of saline solution-filled carbon nanotubes [J].
Gao, Xiang ;
Zhang, Fujian ;
Hu, Xinghao ;
Zhang, Zhongqiang .
JOURNAL OF PHYSICS D-APPLIED PHYSICS, 2022, 55 (21)
[27]   Flexible piezoelectric PVDF/TPU nanofibrous membranes produced by solution blow spinning [J].
Le, Bao ;
Omran, Nada ;
Hassanin, Ahmed H. ;
Kandas, Ishac ;
Gamal, Mohammed ;
Shehata, Nader ;
Shyha, Islam .
JOURNAL OF MATERIALS RESEARCH AND TECHNOLOGY-JMR&T, 2023, 24 :5032-5041
[28]   Intrinsic characteristics of cellulose dissolved in an ionic liquid: the shape of a single cellulose molecule in solution [J].
Koide, Mitsuharu ;
Wataoka, Isao ;
Urakawa, Hiroshi ;
Kajiwara, Kanji ;
Henniges, Ute ;
Rosenau, Thomas .
CELLULOSE, 2019, 26 (04) :2233-2242
[29]   Solution structure of Plasmodium falciparum Hsp90 indicates a high flexible dimer [J].
Silva, Noeli S. M. ;
Torricillas, Marcela S. ;
Minari, Karine ;
Barbosa, Leandro R. S. ;
Seraphim, Thiago, V ;
Borges, Julio C. .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2020, 690
[30]   Flexible field-effect transistors from a liquid crystalline semiconductor by solution processes [J].
Zhang, Fapei ;
Funahashi, Masahiro ;
Tamaoki, Nobuyuki .
ORGANIC ELECTRONICS, 2010, 11 (03) :363-368