Membrane interactions of intrinsically disordered proteins: The example of alpha-synuclein

Das, Tapojyoti; Eliezer, David

doi:10.1016/j.bbapap.2019.05.001

Cited by 47 publications

(52 citation statements)

References 182 publications

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“…Центральный домен является амилоидогенным и может приводить к агрегации белка. C-конец белка состоит из заряженных остатков аминокислот, подвергается посттрансляционным модификациям, опосредует связь альфа-синуклеина с другими белками, лигандами и ионами металлов, а также его шаперонную активность [60,61]. Альфа-синуклеин присутствует в клетке в двух формах: в нативной, в виде растворимого несвернутого белка, и в мембраносвязанной, что сопровождается конформационным переходом в альфа-спираль [62].…”

Section: альфа-синуклеинunclassified

Immunohistochemical markers for neurobiology

Коржевский

Эдуардович²,

Grigor’ev

et al. 2020

Medical academic journal

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In neurobiological studies, crucial is the selection of most appropriate and informative experimental methods, one of which is immunohistochemistry. This review briefly summarizes the experience of adaptation of immunohistochemical methods to nervous system studies accumulated over years the Laboratory of Functional Morphology of the Central and Peripheral Nervous System (Institute of Experimental Medicine). The aim of this work was to determine the most effective and reliable immunomarkers for neurobiological studies. The article contains theoretical basis and practical recommendations for use of key cytospecific and functional markers used in studies of structural and functional organization of brain and spinal cord of mammalian animals and human. In particular, the results of immunohistochemical reactions to neural markers (NeuN, neurofilament proteins, alpha-tubulin, alpha-synuclein), neurotransmitter synthesizing enzymes (tyrosine hydroxylase, glutamate decarboxylase, choline acetyltransferase, NO synthase) and glial markers (GFAP, glutamine synthetase, Iba-1, vimentin) are demonstrated. The presented methodology is useful for experimental neurobiology and clinical morphological diagnostics.

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Section: альфа-синуклеинunclassified

Immunohistochemical markers for neurobiology

Коржевский

Эдуардович²,

Grigor’ev

et al. 2020

Medical academic journal

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“…characterized at the residue level. The most intensely studied protein in this regard is αsynuclein, which forms amphipathic α-helices in the first 100 residues upon membrane association 9 . α-Synuclein preferentially binds to vesicles containing acidic lipids 14 , but membrane curvature also plays an important role.…”

Section: Very Few Fuzzy Complexes Between Disordered Proteins and Memmentioning

confidence: 99%

“…The "extreme" fuzzy complexes in the latter case have been characterized when the partners are another disordered protein or a nucleic acid [1][2][3][4][5] . A third class of partners for disordered proteins comprise membranes [6][7][8][9] . In a well-characterized case, membrane association of α-synuclein is accompanied by the formation of an amphipathic α-helix 9 .…”

Section: Introductionmentioning

confidence: 99%

“…A third class of partners for disordered proteins comprise membranes [6][7][8][9] . In a well-characterized case, membrane association of α-synuclein is accompanied by the formation of an amphipathic α-helix 9 . A large fraction of transmembrane and peripheral membrane proteins contain disordered regions 10 , but there is little knowledge on any extreme fuzzy complexes with membranes.…”

Section: Introductionmentioning

confidence: 99%

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Extreme Fuzzy Association of an Intrinsically Disordered Protein with Acidic Membranes

Hicks

Escobar

Cross

et al. 2020

Preprint

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Many physiological and pathophysiological processes, including Mycobacterium tuberculosis (Mtb) cell division, may involve fuzzy membrane association by proteins via intrinsically disordered regions. The fuzziness is extreme when the conformation and pose of the bound protein and the composition of the proximal lipids are all highly dynamic. Here we tackled the challenge in characterizing the extreme fuzzy membrane association of the disordered, cytoplasmic N-terminal region (NT) of ChiZ, an Mtb divisome protein, by combining solution and solid-state NMR spectroscopy and molecular dynamics simulations. In a typical pose, NT is anchored to acidic membranes by Arg residues in the midsection. Competition for Arg interactions between lipids and acidic residues, all in the first half of NT, makes the second half more prominent in membrane association. This asymmetry is accentuated by membrane tethering of the downstream transmembrane helix. These insights into sequence-interaction relations may serve as a paradigm for understanding fuzzy membrane association.

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“…While folded conformations are typically unique and well defined, the "open" or unfolded forms are represented by ensembles of multiple alternative conformers. Intrinsically disordered proteins (IDP) are one example where multiple unfolded or partially folded polypeptide conformations are in exchange, and the ligand interacts with a matching one-often followed by an additional induced-fit transition to the tightly bound state [1][2][3] . Another situation with multiple alternative conformations arises when a protein structure undergoes a conformational transition ("opening"; local unfolding) to allow for the ligand binding, and the ligand will induce a new stable conformation.…”

Section: Introductionmentioning

confidence: 99%

NMR Line Shapes in Molecular Mechanisms with Ligand Binding and Multiple Conformers

Kovrigin

2020

Preprint

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Interactions of ligands with biological macromolecules are sensitively detected through changes of chemical shifts and line shapes of the NMR signals. This paper reports a mathematical analysis and simulations of NMR line shapes expected in titrations when ligand binding is coupled to multiple isomerization transitions. Such molecular mechanisms may correspond to ligand binding by intrinsically disordered proteins or by autoinhibited enzymes. Based on the simulation results, we anticipate several specific effects that may be observed in practice. First, the presence of non-binding conformers of the receptor molecule leads to a remarkable broadening in the binding transition even if the exchange between binding and non-binding conformers is very slow. Second, the ligand-binding mechanisms involving induced fit are expected to demonstrate deceptively decelerated exchange regimes even when the underlying kinetics are very fast. Conversely, the observation of fast-exchange shifting resonances with modest line-broadening ("marching peaks") in practical NMR titrations may involve conformational selection transitions but less likely to be observed for the induced fit. Finally, in autoinhibited molecules that open to form multiple binding-competent conformers, the fast dynamics of opening/closing transition are capable of masking the true kinetics of interconversion among transiently open forms of the receptor.

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Membrane interactions of intrinsically disordered proteins: The example of alpha-synuclein

Cited by 47 publications

References 182 publications

Immunohistochemical markers for neurobiology

Immunohistochemical markers for neurobiology

Extreme Fuzzy Association of an Intrinsically Disordered Protein with Acidic Membranes

NMR Line Shapes in Molecular Mechanisms with Ligand Binding and Multiple Conformers

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