The BG21 isoform of Golli myelin basic protein is intrinsically disordered with a highly flexible amino-terminal domain

被引:16
作者
Ahmed, Mumdooh A. M.
Bamm, Vladimir V.
Harauz, George
Ladizhansky, Vladimir
机构
[1] Univ Guelph, Dept Phys & Biophys Interdept Grp, Guelph, ON N1G 2W1, Canada
[2] Univ Guelph, Dept Mol & Cell Biol & Biophys Interdept Grp, Guelph, ON N1G 2W1, Canada
关键词
D O I
10.1021/bi700632x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The genes of the oligodendrocyte lineage (Golli) encode a family of developmentally regulated isoforms of myelin basic protein. The "classic" MBP isoforms arise from transcription start site 3, whereas Golli-specific isoforms arise from transcription start site 1, and comprise both Golli-specific and classic MBP sequences. The Golli isoform BG21 has been suggested to play roles in myelination and T cell activation pathways. It is an intrinsically disordered protein, thereby presenting a large effective surface area for interaction with other proteins such as Golli-interacting protein. We have used multidimensional heteronuclear NMR spectroscopy to achieve sequence-specific resonance assignments of the recombinant murine BG21 in physiologically relevant buffer, to analyze its secondary structure using chemical shift indexing (CSI), and to investigate its backbone dynamics using N-15 spin relaxation measurements. We have assigned 184 out of 199 residues unambiguously. The CSI analysis revealed little ordered secondary structure under these conditions, with only some small fragments having a slight tendency toward alpha-helicity, which may represent putative recognition motifs. The N-15 relaxation and NOE measurements confirmed the general behavior of the protein as an extended polypeptide chain, with the N-terminal Golli-specific portion (residues S5-T69) being exceptionally flexible, even in comparison to other intrinsically disordered proteins that have been studied this way. The high degree of flexibility of this N-terminal region may be to provide additional plasticity, or conformational adaptability, in protein-protein interactions. Another highly mobile segment, A126-S127-G128-G129, may function as a hinge.
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页码:9700 / 9712
页数:13
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