RRC ID 57702
Author Sumi T, Imasaki T, Aoki M, Sakai N, Nitta E, Shirouzu M, Nitta R.
Title Structural Insights into the Altering Function of CRMP2 by Phosphorylation.
Journal Cell Struct Funct
Abstract Collapsin response mediator protein 2 (CRMP2) regulates neuronal polarity by controlling microtubule dynamics. CRMP2 activity is regulated by semaphorin-induced phosphorylation at the C-terminal tail domain. Unphosphorylated CRMP2 induces effective axonal microtubule formation to give the axonal characteristics to a neurite, whereas phosphorylated CRMP2 leads to the apparently opposite effect, growth cone collapse. We have recently characterized the structural detail of CRMP2-induced axonal microtubule formation (Niwa et al. (2017) Sci. Rep., 7: 10681). CRMP2 forms the hetero-trimer with GTP-tubulin to induce effective axonal microtubule formation in the future axon. Phosphorylation of CRMP2 has been reported to decrease the affinity between CRMP2 and the microtubule, albeit the molecular mechanisms of how the phosphorylation of CRMP2 changes the structure to achieve distinct effects from unphosphorylated CRMP2 is not well understood. Here we performed a series of biochemical and structural analyses of phospho-mimic CRMP2. Phosphorylation of CRMP2 undergoes small conformational changes at the C-terminal tail with shifting the surface charge, which not only alters the interactions within the CRMP2 tetramer but also alters the interactions with GTP-tubulin. Consequently, phospho-mimic CRMP2 fails to form a hetero-trimer with GTP-tubulin, thus losing the ability to establish and maintain the axonal microtubules.Key words: CRMP2, phosphorylation, microtubule, axon, crystal structure.
Volume 43(1)
Pages 15-23
Published 2018
DOI 10.1247/csf.17025
PMID 29479005
MeSH Amino Acid Sequence Crystallography, X-Ray Dynamic Light Scattering Glycogen Synthase Kinase 3 beta / chemistry Glycogen Synthase Kinase 3 beta / metabolism Guanosine Triphosphate / metabolism Humans Intercellular Signaling Peptides and Proteins / chemistry* Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* Microtubules / metabolism Molecular Dynamics Simulation Nerve Tissue Proteins / chemistry* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Phosphorylation Protein Structure, Quaternary Recombinant Proteins / biosynthesis Recombinant Proteins / chemistry Recombinant Proteins / isolation & purification Recombinant Proteins / metabolism Sequence Alignment Tubulin / chemistry Tubulin / metabolism
IF 3.5
Times Cited 8
Resource
DNA material CP525-S522D (RDB17507) CP525-4D (RDB17508) GST-CP525 (RDB17509)