scholarly journals Myelin Basic Protein dynamics from out-of-equilibrium functional state to degraded state in myelin

2019 ◽  
Author(s):  
M. Di Gioacchino ◽  
A. Bianconi ◽  
M. Burghammer ◽  
G. Ciasca ◽  
F. Bruni ◽  
...  
Keyword(s):  
Myelin Basic Protein ◽  
Protein Dynamics ◽  
Functional State ◽  
Structural Dynamics ◽  
Basic Protein ◽  
Physiological State ◽  
X Ray ◽  
Intrinsically Disordered ◽  
Protein Structural Dynamics

ABSTRACTLiving matter is a quasi-stationary out-of-equilibrium system; in this physical condition, structural fluctuations at nano- and meso-scales are needed to understand the physics behind its biological functionality. Myelin has a simple ultrastructure whose fluctuations show correlated disorder in its functional out-of-equilibrium state. However, there is no information on the relationship between this correlated disorder and the dynamics of the intrinsically disordered Myelin Basic Protein (MBP) which is expected to influence the membrane structure and overall functionality. In this work, we have investigated the role of this protein structural dynamics in the myelin ultrastructure fluctuations in and out-of-equilibrium conditions, by using synchrotron Scanning micro X Ray Diffraction and Small Angle X ray Scattering. We have induced the crossover from out-of-equilibrium functional state to in-equilibrium degeneration changing the pH far away from physiological condition. While the observed compression of the cytosolic layer thickness probes the unfolding of the P2 protein and of the cytoplasmic P0 domain (P0cyt), the intrinsic large MBP fluctuations preserve the cytosol structure also in the degraded state. Thus, the transition of myelin ultrastructure from correlated to uncorrelated disordered state, is significantly affected by the unfolding of the P2 and P0 proteins, which in this latter state do not act in synergistic manner with MBP to determine the membrane functionality.STATEMENT OF SIGNIFICANCEA better comprehension of myelin degenerative process and the role of protein dynamics in this biological membrane is a topic issue in today’s scientific community. The myelin ultrastructural fluctuations exhibit correlated disorder in its functional state, that becomes uncorrelated as it degenerates. In this work we elucidate the interplay of protein structural dynamics and myelin ultrastructure in the transition from its functional state to the degraded state. The results highlight that the intrinsically disordered Myelin Basic Protein (MBP) allows to preserve the myelin structure following both the small correlated fluctuations in physiological state and the large disordered fluctuations in degraded conditions, where the myelin functionality is close to being lost and the MBP remains the single active protein.

scholarly journals Myelin basic protein dynamics from out-of-equilibrium functional state to degraded state in myelin

2020 ◽  
Vol 1862 (6) ◽  
pp. 183256 ◽  
Author(s):  
Michael Di Gioacchino ◽  
Antonio Bianconi ◽  
Manfred Burghammer ◽  
Gabriele Ciasca ◽  
Fabio Bruni ◽  
...  
Keyword(s):  
Myelin Basic Protein ◽  
Protein Dynamics ◽  
Functional State ◽  
Basic Protein

scholarly journals Fuzzy complexes of myelin basic protein: NMR spectroscopic investigations of a polymorphic organizational linker of the central nervous systemThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (2) ◽  
pp. 143-155 ◽  
Author(s):  
David S. Libich ◽  
Mumdooh A.M. Ahmed ◽  
Ligang Zhong ◽  
Vladimir V. Bamm ◽  
Vladimir Ladizhansky ◽  
...  
Keyword(s):  
Solid State ◽  
Myelin Basic Protein ◽  
Solid State Nmr ◽  
Basic Protein ◽  
Peer Review Process ◽  
Protein Nmr ◽  
Spectroscopic Studies ◽  
Intrinsically Disordered ◽  
The Central Nervous System ◽  
Structural Homeostasis

The classic 18.5 kDa isoform of myelin basic protein (MBP) is central to maintaining the structural homeostasis of the myelin sheath of the central nervous system. It is an intrinsically disordered, promiscuous, multifunctional, peripheral membrane protein, whose conformation adapts to its particular environment. Its study requires the selective and complementary application of diverse approaches, of which solution and solid-state NMR spectroscopy are the most powerful to elucidate site-specific features. We review here several recent solution and solid-state NMR spectroscopic studies of 18.5 kDa MBP, and the induced partial disorder-to-order transitions that it has been demonstrated to undergo when complexed with calmodulin, actin, and phospholipid membranes.

MyelStones: the executive roles of myelin basic protein in myelin assembly and destabilization in multiple sclerosis

2015 ◽  
Vol 472 (1) ◽  
pp. 17-32 ◽  
Author(s):  
Kenrick A. Vassall ◽  
Vladimir V. Bamm ◽  
George Harauz
Keyword(s):  
Multiple Sclerosis ◽  
Myelin Basic Protein ◽  
Intrinsically Disordered Proteins ◽  
Basic Protein ◽  
Disordered Proteins ◽  
Post Translational Modifications ◽  
Src Homology 3 ◽  
Intrinsically Disordered ◽  
Src Homology ◽  
Membrane Anchoring

The classic isoforms of myelin basic protein (MBP, 14–21.5 kDa) are essential to formation of the multilamellar myelin sheath of the mammalian central nervous system (CNS). The predominant 18.5-kDa isoform links together the cytosolic surfaces of oligodendrocytes, but additionally participates in cytoskeletal turnover and membrane extension, Fyn-mediated signalling pathways, sequestration of phosphoinositides and maintenance of calcium homoeostasis. All MBP isoforms are intrinsically disordered proteins (IDPs) that interact via molecular recognition fragments (MoRFs), which thereby undergo local disorder-to-order transitions. Their conformations and associations are modulated by environment and by a dynamic barcode of post-translational modifications, particularly phosphorylation by mitogen-activated and other protein kinases and deimination [a hallmark of demyelination in multiple sclerosis (MS)]. The MBPs are thus to myelin what basic histones are to chromatin. Originally thought to be merely structural proteins forming an inert spool, histones are now known to be dynamic entities involved in epigenetic regulation and diseases such as cancer. Analogously, the MBPs are not mere adhesives of compact myelin, but active participants in oligodendrocyte proliferation and in membrane process extension and stabilization during myelinogenesis. A central segment of these proteins is pivotal in membrane-anchoring and SH3 domain (Src homology 3) interaction. We discuss in the present review advances in our understanding of conformational conversions of this classic basic protein upon membrane association, including new thermodynamic analyses of transitions into different structural ensembles and how a shift in the pattern of its post-translational modifications is associated with the pathogenesis and potentially onset of demyelination in MS.

scholarly journals Role of Very-late Antigen-4 (VLA-4) in Myelin Basic Protein-primed T Cell Contact-induced Expression of Proinflammatory Cytokines in Microglial Cells

2003 ◽  
Vol 278 (25) ◽  
pp. 22424-22431 ◽  
Author(s):  
Subhajit Dasgupta ◽  
Malabendu Jana ◽  
Xiaojuan Liu ◽  
Kalipada Pahan
Keyword(s):  
T Cell ◽  
Myelin Basic Protein ◽  
Proinflammatory Cytokines ◽  
Basic Protein ◽  
Microglial Cells ◽  
Cell Contact ◽  
Induced Expression ◽  
Late Antigen

Structural Dynamics of Myelin Basic Protein in the Assembly of a Model Membrane

1989 ◽  
pp. 383-388 ◽  
Author(s):  
P. Cavatorta ◽  
L. Masotti ◽  
A. G. Szabo ◽  
P. Riccio ◽  
E. Quagliariello
Keyword(s):  
Myelin Basic Protein ◽  
Structural Dynamics ◽  
Basic Protein ◽  
Model Membrane

Role of phosphorylation in conformational adaptability of bovine myelin basic protein

1990 ◽  
Vol 7 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Gladys E. Deibler ◽  
Audrey L. Stone ◽  
Marian W. Kies
Keyword(s):  
Myelin Basic Protein ◽  
Basic Protein

scholarly journals Role of Computational Methods in Going beyond X-ray Crystallography to Explore Protein Structure and Dynamics

2018 ◽  
Vol 19 (11) ◽  
pp. 3401 ◽  
Author(s):  
Ashutosh Srivastava ◽  
Tetsuro Nagai ◽  
Arpita Srivastava ◽  
Osamu Miyashita ◽  
Florence Tama
Keyword(s):  
Protein Dynamics ◽  
Computational Methods ◽  
Protein Structures ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
X Ray ◽  
X Ray Crystallography ◽  
Insight Into

Protein structural biology came a long way since the determination of the first three-dimensional structure of myoglobin about six decades ago. Across this period, X-ray crystallography was the most important experimental method for gaining atomic-resolution insight into protein structures. However, as the role of dynamics gained importance in the function of proteins, the limitations of X-ray crystallography in not being able to capture dynamics came to the forefront. Computational methods proved to be immensely successful in understanding protein dynamics in solution, and they continue to improve in terms of both the scale and the types of systems that can be studied. In this review, we briefly discuss the limitations of X-ray crystallography in studying protein dynamics, and then provide an overview of different computational methods that are instrumental in understanding the dynamics of proteins and biomacromolecular complexes.

scholarly journals Myelin Basic Protein-Specific TCR/HLA-DRB5*01:01 Transgenic Mice Support the Etiologic Role of DRB5*01:01 in Multiple Sclerosis

2012 ◽  
Vol 189 (6) ◽  
pp. 2897-2908 ◽  
Author(s):  
Jacqueline A. Quandt ◽  
Jaebong Huh ◽  
Mirza Baig ◽  
Karen Yao ◽  
Naoko Ito ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Transgenic Mice ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Etiologic Role
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