2LUG

Solution NMR structure of a S72-S107 peptide of 18.5kDa murine myelin basic protein (MBP) in association with dodecylphosphocholine micelles

2LUG の概要

• エントリーDOI: 10.2210/pdb2lug/pdb
• NMR情報: BMRB: 18520
• 分子名称: Myelin basic protein (1 entity in total)
• 機能のキーワード: intrinsically disordered proteins, dodecylphosphocholine micelles, myelin membrane, lipid binding protein
• 由来する生物種: Mus musculus (mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3977.42

構造登録者

Ahmed, M.A.M.,De Avila, M.,Polverini, E.,Bessonov, K.,Bamm, V.V.,Harauz, G. (登録日: 2012-06-13, 公開日: 2012-09-19, 最終更新日: 2024-05-15)

主引用文献

Ahmed, M.A.,De Avila, M.,Polverini, E.,Bessonov, K.,Bamm, V.V.,Harauz, G.
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.
Biochemistry, 51:7475-7487, 2012

PubMed Abstract: 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.

PubMed: 22947219
DOI: 10.1021/bi300998x

実験手法

SOLUTION NMR