Juxtanodin is an intrinsically disordered F-actin-binding protein

Ruskamo, Salla; Chukhlieb, Maryna; Vahokoski, Juha; Bhargav, Saligram Prabhakar; Liang, Fengyi; Kursula, Inari; Kursula, Petri

doi:10.1038/srep00899

Cited by 30 publications

(42 citation statements)

References 57 publications

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“…In recent years, long-held protein structure-function paradigms have been challenged by the characterization of a number of IDPs. Notably, as an addition to this group of IDPs, we have recently characterized the oligodendrocytic microfilament-binding protein juxtanodin as intrinsically disordered [106]. In addition, many myelin proteins, such as periaxin, MOBP, and the MAG cytoplasmic domains, contain long stretches predicted to be disordered ( Fig.…”

Section: Common Structural and Functional Featuresmentioning

confidence: 99%

“…It is possible that also other myelin proteins, in addition to MBP, present large conformational changes upon interacting with lipid membrane surfaces. Notably, as an addition to this group of IDPs, we have recently characterized the oligodendrocytic microfilament-binding protein juxtanodin as intrinsically disordered [106].…”

Section: Common Structural and Functional Featuresmentioning

confidence: 99%

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Myelin‐specific proteins: A structurally diverse group of membrane‐interacting molecules

et al. 2013

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The myelin sheath is a multilayered membrane in the nervous system, which has unique biochemical properties. Myelin carries a set of specific high-abundance proteins, the structure and function of which are still poorly understood. The proteins of the myelin sheath are involved in a number of neurological diseases, including autoimmune diseases and inherited neuropathies. In this review, we briefly discuss the structural properties and functions of selected myelin-specific proteins (P0, myelin oligodendrocyte glycoprotein, myelin-associated glycoprotein, myelin basic protein, myelin-associated oligodendrocytic basic protein, P2, proteolipid protein, peripheral myelin protein of 22 kDa, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and periaxin); such properties include, for example, interactions with lipid bilayers and the presence of large intrinsically disordered regions in some myelin proteins. A detailed understanding of myelin protein structure and function at the molecular level will be required to fully grasp their physiological roles in the myelin sheath.

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Section: Common Structural and Functional Featuresmentioning

confidence: 99%

Section: Common Structural and Functional Featuresmentioning

confidence: 99%

Myelin‐specific proteins: A structurally diverse group of membrane‐interacting molecules

et al. 2013

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“…Juxtanodin (Jux; also called ermin) is a monomeric 280-residue oligodendrocytic IDP localized in the juxtaparanodes of adaxonal non-compact myelin [160][161][162]. Jux is involved in the morphological regulation of oligodendrocytes, more specifically in the formation of arborizations [161][162][163].…”

Section: Juxtanodinmentioning

confidence: 99%

“…Jux associates with the cytoskeleton, and the association is negatively regulated through phosphorylation [164]. The interaction involves filamentous actin, and has been shown to be solely dependent on the C-terminal ezrin/radixin/moesin (ERM)-type F-actin-binding domain, which is the only region of Jux to share any homology with other proteins [160,164]. This domain is comprised of 30 amino acids, and is the most conserved region in Jux ( Figure 5); the last 14 residues are crucial for the actin interaction [160,164].…”

Section: Juxtanodinmentioning

confidence: 99%

Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease

Raasakka

Kursula

2020

Preprint

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Myelin ensheathes selected axonal segments within the nervous system, resulting primarily in nerve impulse acceleration, as well as mechanical and trophic support for neurons. In the central and peripheral nervous systems, various proteins that contribute to the formation and stability of myelin are present, which also harbour pathophysiological roles in myelin disease. Many myelin proteins share common attributes, including small size, high hydrophobicity, multifunctionality, longevity, and intrinsic disorder. With recent advances in protein biophysical characterization and bioinformatics, it has become evident that intrinsically disordered proteins (IDPs) are abundant in myelin, and their flexible nature enables multifunctionality. Here, we review known myelin IDPs, their conservation, molecular characteristics and functions, and their disease relevance, along with open questions and speculations. We place emphasis on classifying the molecular details of IDPs in myelin and correlate these with their various functions, including susceptibility to post-translational modifications, function in protein-protein and protein-membrane interactions, as well as their role as extended entropic chains. We discuss how myelin pathology can relate to IDPs and which molecular factors are potentially involved.

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“…Because A2A-ctL behaved like an intrinsically disordered protein, its radius of gyration was also determined using the Debye formalism (54). Furthermore, the expected dimensions based on a random conformation were calculated as described (55,56).…”

Section: Small-angle X-ray Scattering (Saxs)mentioning

confidence: 99%

Human Adenosine A2A Receptor Binds Calmodulin with High Affinity in a Calcium-Dependent Manner

Piirainen

Hellman

Tossavainen

et al. 2015

Biophysical Journal

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Understanding how ligands bind to G-protein-coupled receptors and how binding changes receptor structure to affect signaling is critical for developing a complete picture of the signal transduction process. The adenosine A2A receptor (A2AR) is a particularly interesting example, as it has an exceptionally long intracellular carboxyl terminus, which is predicted to be mainly disordered. Experimental data on the structure of the A2AR C-terminus is lacking, because published structures of A2AR do not include the C-terminus. Calmodulin has been reported to bind to the A2AR C-terminus, with a possible binding site on helix 8, next to the membrane. The biological meaning of the interaction as well as its calcium dependence, thermodynamic parameters, and organization of the proteins in the complex are unclear. Here, we characterized the structure of the A2AR C-terminus and the A2AR C-terminus-calmodulin complex using different biophysical methods, including native gel and analytical gel filtration, isothermal titration calorimetry, NMR spectroscopy, and small-angle X-ray scattering. We found that the C-terminus is disordered and flexible, and it binds with high affinity (Kd = 98 nM) to calmodulin without major conformational changes in the domain. Calmodulin binds to helix 8 of the A2AR in a calcium-dependent manner that can displace binding of A2AR to lipid vesicles. We also predicted and classified putative calmodulin-binding sites in a larger group of G-protein-coupled receptors.

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Juxtanodin is an intrinsically disordered F-actin-binding protein

Cited by 30 publications

References 57 publications

Myelin‐specific proteins: A structurally diverse group of membrane‐interacting molecules

Myelin‐specific proteins: A structurally diverse group of membrane‐interacting molecules

Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease

Human Adenosine A2A Receptor Binds Calmodulin with High Affinity in a Calcium-Dependent Manner

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