Structure and function of the proline-rich region of myelin basic protein

Fraser, Paul E.; Deber, Charles M.

doi:10.1021/bi00338a017

Cited by 24 publications

(11 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Briefly, it comprised an amphipathic α-helix from residue E80 to residue V91 and an extended strand in a left-handed polyproline type II (PPII) conformation from residue T92 to residue G103. All prolyl residues were in the trans configuration. , We henceforth refer to this in silico construct as the MD-peptide to distinguish it from the real, in vitro, α2-peptide.…”

Section: Methodsmentioning

confidence: 99%

Solution Nuclear Magnetic Resonance Structure and Molecular Dynamics Simulations of a Murine 18.5 kDa Myelin Basic Protein Segment (S72–S107) in Association with Dodecylphosphocholine Micelles

Ahmed

Avila²,

Polverini

et al. 2012

Biochemistry

View full text Add to dashboard Cite

The 18.5 kDa myelin basic protein (MBP), the most abundant splice isoform in adult mammalian myelin, is a multifunctional, intrinsically disordered protein involved in the development and compaction of the myelin sheath in the central nervous system. A highly conserved central segment comprises a membrane-anchoring amphipathic α-helix followed by a proline-rich segment that represents a ligand for SH3 domain-containing proteins. Here, we have determined using solution nuclear magnetic resonance spectroscopy the structure of a 36-residue peptide fragment of MBP (murine 18.5 kDa residues S72-S107, denoted the α2-peptide) comprising these two structural motifs, in association with dodecylphosphocholine (DPC) micelles. The structure was calculated using CS-ROSETTA (version 1.01) because the nuclear Overhauser effect restraints were insufficient for this protein. The experimental studies were complemented by molecular dynamics simulations of a corresponding 24-residue peptide fragment (murine 18.5 kDa residues E80-G103, denoted the MD-peptide), also in association with a DPC micelle in silico. The experimental and theoretical results agreed well with one another, despite the independence of the starting structures and analyses, both showing membrane association via the amphipathic α-helix, and a sharp bend in the vicinity of the Pro93 residue (murine 18.5 kDa sequence numbering). Overall, the conformations elucidated here show how the SH3 ligand is presented to the cytoplasm for interaction with SH3 domain-containing proteins such as Fyn and contribute to our understanding of myelin architecture at the molecular level.

show abstract

Section: Methodsmentioning

confidence: 99%

Solution Nuclear Magnetic Resonance Structure and Molecular Dynamics Simulations of a Murine 18.5 kDa Myelin Basic Protein Segment (S72–S107) in Association with Dodecylphosphocholine Micelles

Ahmed

Avila²,

Polverini

et al. 2012

Biochemistry

View full text Add to dashboard Cite

show abstract

“…The major sites of modification are Thr-95 and Thr-98 (O-glycosidic bond) which are in the vicinity of the unusual tri-proline region 99-101. These proline residues have been found, through the use of synthetic peptides, to represent an essential sequence for the transfer of the GalNAc group and may possibly confer a preferential conformation upon this region of MBP (126)(127)(128). However, the function, if any, of this modification is as yet unknown and it remains to be determined if this glycosylation process occurs in vivo.…”

Section: Glycosylationmentioning

confidence: 99%

Central nervous system myelin: structure, function, and pathology

Deber

Reynolds

1991

Clinical Biochemistry

Self Cite

109

View full text Add to dashboard Cite

Multiple sclerosis (MS) and a number of related distinctive diseases are characterized by the active degradation of central nervous system (CNS) myelin, an axonal sheath comprised essentially of proteins and lipids. These demyelinating diseases appear to arise from complex interactions of genetic, immunological, infective, and biochemical mechanisms. While circumstances of MS etiology remain hypothetical, one persistent theme involves recognition by the immune system of myelin-specific antigens derived from myelin basic protein (MBP), the most abundant extrinsic myelin membrane protein, and/or another equally susceptible myelin protein or lipid component. Knowledge of the biochemical and physical-chemical properties of myelin proteins and lipids, particularly their composition, organization, structure, and accessibility with respect to the compacted myelin multilayers, thus becomes central to the understanding of how and why these antigens become selected during the development of MS. This review focuses on current understanding of the molecular basis underlying demyelinating disease as it may relate to the impact of the various protein and lipid components on myelin morphology; the precise molecular architecture of this membrane as dictated by protein-lipid and lipid-lipid interactions; and the relationship, if any, between the protein/lipid components and the destruction of myelin in pathological situations.

show abstract

“…Comparable plots were also generated with both decision constants set at 0: For shark, these values resulted in extension of the a-helical region shown above and generation of an additional stretch containing 10 amino acids near residue 80. (Brostoff and Eylar,197 I), although subsequent nuclear magnetic resonance experiments have failed to confirm the presence of such a structure (Nygaard et al, 1984;Fraser and Deber, 1985). This triproline sequence is absent in shark MBP.…”

Section: Discussionmentioning

confidence: 98%

Shark Myelin Basic Protein: Amino Acid Sequence, Secondary Structure, and Self‐Association

Milne

Atkins

Warren

et al. 1990

Journal of Neurochemistry

View full text Add to dashboard Cite

Myelin basic protein (MBP) from the Whaler shark (Carcharhinus obscurus) has been purified from acid extracts of a chloroform/methanol pellet from whole brains. The amino acid sequence of the majority of the protein has been determined and compared with the sequences of other MBPs. The shark protein has only 44% homology with the bovine protein, but, in common with other MBPs, it has basic residues distributed throughout the sequence and no extensive segments that are predicted to have an ordered secondary structure in solution. Shark MBP lacks the triproline sequence previously postulated to form a hairpin bend in the molecule. The region containing the putative consensus sequence for encephalitogenicity in the guinea pig contains several substitutions, thus accounting for the lack of activity of the shark protein. Studies of the secondary structure and self-association have shown that shark MBP possesses solution properties similar to those of the bovine protein, despite the extensive differences in primary structure.

show abstract

Structure and function of the proline-rich region of myelin basic protein

Cited by 24 publications

References 23 publications

Solution Nuclear Magnetic Resonance Structure and Molecular Dynamics Simulations of a Murine 18.5 kDa Myelin Basic Protein Segment (S72–S107) in Association with Dodecylphosphocholine Micelles

Solution Nuclear Magnetic Resonance Structure and Molecular Dynamics Simulations of a Murine 18.5 kDa Myelin Basic Protein Segment (S72–S107) in Association with Dodecylphosphocholine Micelles

Central nervous system myelin: structure, function, and pathology

Shark Myelin Basic Protein: Amino Acid Sequence, Secondary Structure, and Self‐Association

Contact Info

Product

Resources

About