Myelin basic protein binds GTP at a single site in the N-terminus

Chan, Khai-Chew; Ranwani, J.; Moscarello, Mario A.

doi:10.1016/s0006-291x(88)80451-0

Cited by 32 publications

(27 citation statements)

References 19 publications

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“…In many cases, these post-translational modifications are thought to regulate myelin assembly, MBP-ligand interactions, and signaling functions (71). MBP interacts with many different ligands, including lipids (69,72), calmodulin (73), divalent cations (74), GTP (75), and cytoskeletal proteins such as tubulin (76) and actin (77). The binding of MBP to tubulin and actin is believed to stabilize their polymerization, which is essential to the formation of myelin sheaths (78).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Familial Cerebral Amyloid Angiopathy Mutant Amyloid β-Protein Fibril Assembly by Myelin Basic Protein

Hoos

Ahmed

Smith

et al. 2007

Journal of Biological Chemistry

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Deposition of fibrillar amyloid ␤-protein (A␤) in the brain is a prominent pathological feature of Alzheimer disease and related disorders, including familial forms of cerebral amyloid angiopathy (CAA). Mutant forms of A␤, including Dutch-and Iowa-type A␤, which are responsible for familial CAA, deposit primarily as fibrillar amyloid along the cerebral vasculature and are either absent or present only as diffuse non-fibrillar plaques in the brain parenchyma. Despite the lack of parenchymal fibril formation in vivo, these CAA mutant A␤ peptides exhibit a markedly increased rate and extent of fibril formation in vitro compared with wild-type A␤. Based on these conflicting observations, we sought to determine whether brain parenchymal factors that selectively interact with and modulate CAA mutant A␤ fibril assembly exist. Using a combination of immunoaffinity chromatography and mass spectrometry, we identified myelin basic protein (MBP) as a prominent brain parenchymal factor that preferentially binds to CAA mutant A␤ compared with wild-type A␤. Surface plasmon resonance measurements confirmed that MBP bound more tightly to Dutch/Iowa CAA double mutant A␤ than to wild-type A␤. Using a combination of biochemical and ultrastructural techniques, we found that MBP inhibited the fibril assembly of CAA mutant A␤. Together, these findings suggest a possible role for MBP in regulating parenchymal fibrillar A␤ deposition in familial CAA. Extracellular deposition of amyloid ␤-protein (A␤)2 in the brain is a prominent feature of Alzheimer disease and other related disorders (1). A␤ is a 39 -43-amino acid peptide that exhibits a high propensity to self-assemble into ␤-sheet-containing oligomeric forms and fibrils (2). A␤ peptides are proteolytically produced from the amyloid ␤-protein precursor (A␤PP), a large type I integral membrane protein, through sequential proteolysis by ␤-and ␥-secretase activities (3-6). Cerebral deposition of A␤ in the parenchyma can occur as diffuse plaques, with little surrounding pathology, or as fibrillar plaques associated with dystrophic neurons, neurofibrillary tangles, and inflammation (1). Fibrillar A␤ deposition also occurs within and along primarily small and medium arteries and arterioles of the cerebral cortex and leptomeninges and in the cerebral microvasculature, a condition known as cerebral amyloid angiopathy (CAA) (7-9). This condition accounts for up to 20% of all spontaneous primary intracerebral hemorrhages and is a key pathological lesion in nearly all patients with Alzheimer disease and certain related disorders. Accumulation of fibrillar cerebral vascular A␤ has been shown to cause degeneration and cell death of smooth muscle cells and pericytes in affected larger cerebral vessels and cerebral microvessels, respectively (9 -11). Recent findings have implicated cerebral microvascular A␤ deposition in promoting neuroinflammation and dementia in Alzheimer disease (12-15).There exist several familial monogenic forms of CAA resulting from specific point mutations within the A␤ seque...

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Section: Discussionmentioning

confidence: 99%

Inhibition of Familial Cerebral Amyloid Angiopathy Mutant Amyloid β-Protein Fibril Assembly by Myelin Basic Protein

Hoos

Ahmed

Smith

et al. 2007

Journal of Biological Chemistry

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“…The analogy to chol A behavior is strengthened by recent reports from the Moscarello laboratory [3], that GTP is bound to the N-terminal region of human MBP and that MBP can also be ADPribosylated [4].…”

mentioning

confidence: 90%

“…The isoelectric point is greater than 10.6 [l], it binds GM~ ganglioside [2], GTP [3], and it can be ADPribosylated [4]. The protein and some of its peptides are highly antigenic, and are capable of inducing experimental allergic encephalomyelitis, EAE, in a number of laboratory animals.…”

Section: Myelin Basic Protein; Cholera Toxin; Sequence Homologymentioning

confidence: 99%

“…The NMR study [2] also implicated this residue in the binding of the GM~ ganglioside. Although the attachment of azido GTP is reported to occur in MBP at glutamine residue 3 [3], the peptide sequence homology with chol A occurs from residues 8 to 20. This small sequence displacement does not detract from the homology that has been identified, since elements of secondary and tertiary structure could influence the placement of the GTP on equivalent glutamines in the region.…”

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confidence: 99%

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Homologous sequences in cholera toxin A and B subunits to peptide domains in myelin basic protein

Caamaño¹,

Zand²

1989

FEBS Letters

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Recent reports that myelin basic protein (MBP) can be ADP-ribosylated and contains specific sites that bind GTP and Gu, ganglioside, have suggested an analogy to the properties of cholera toxin. Comparisons of pairs of sequences between these two proteins yielded two regions of homology between MBP and the cholera toxin B (chol B) subunit, and one region of homology with the cholera toxin A (chol A) subunit. The matching sites within chol B consisted of a 17 amino acid residue sequence (residues 3046 in chol B and residues 102-I 18 in human-MBP, hMBP, p < 0.0007) and an 11 residue span (residues 3141 in chol B and sequence 29-39 in hMBP, p

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“…MBP itself may play a role, however, because MBP's phosphorylation state changes after anti-GalC binding , and phosphorylation is a common mechanism in transducing signals. In addition, MBP has been reported to bind GTP and cholera toxin ribosylated in vitro (Chan et al, 1988).…”

Section: Redistributed Cholesterol Directly Overlies Veinlike Structumentioning

confidence: 99%

Redistribution of cholesterol in oligodendrocyte membrane sheets after activation of distinct signal transduction pathways

Lintner

Dyer

2000

J. Neurosci. Res.

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Cultured oligodendrocytes produce extensive membrane sheets that contain an internal lacy network of vein-like structures composed of microtubules, actin filaments, and 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNPase). These cytoplasmic vein-like structures surround domains of myelin basic protein (MBP). Using the antibiotic filipin, that binds to cholesterol, the relationship between plasma membrane cholesterol and cytoskeleton in membrane sheets was examined. Our results show that cholesterol was relatively uniformly distributed within the plasma membranes of prefixed control oligodendrocyte membrane sheets. When live cultures were extracted with Triton X-100, however, a subpopulation of cholesterol molecules remained colocalized with cytoskeleton in the membrane sheets. Activation of two well-characterized signaling pathways that differentially affect microtubule and actin filament stability in membrane sheets resulted in an apparent massive lateral movement of cholesterol molecules away from membrane regions overlying internal MBP domains to membrane tracts directly overlying cytoplasmic cytoskeletal veins. Depolymerization of microtubules by colchicine resulted in redistribution of cholesterol directly over actin filaments, whereas depolymerization of actin filaments by cytochalasin B resulted in redistribution of cholesterol directly over CNPase/microtubular veins. These data suggest that cholesterol forms an association with cytoskeletal components or proteins associated with cytoskeleton. These data also suggest that cholesterol, via interactions with cytoskeleton, plays a role in signaling pathways in oligodendrocyte membrane sheets.

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Myelin basic protein binds GTP at a single site in the N-terminus

Cited by 32 publications

References 19 publications

Inhibition of Familial Cerebral Amyloid Angiopathy Mutant Amyloid β-Protein Fibril Assembly by Myelin Basic Protein

Inhibition of Familial Cerebral Amyloid Angiopathy Mutant Amyloid β-Protein Fibril Assembly by Myelin Basic Protein

Homologous sequences in cholera toxin A and B subunits to peptide domains in myelin basic protein

Redistribution of cholesterol in oligodendrocyte membrane sheets after activation of distinct signal transduction pathways

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