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Crystal and solution structure, stability and post‐translational modifications of collapsin response mediator protein 2
Author(s) -
Majava Viivi,
Löytynoja Noora,
Chen WeiQiang,
Lubec Gert,
Kursula Petri
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06601.x
Subject(s) - chemistry , biophysics , mediator , calcium , crystallography , biochemistry , microbiology and biotechnology , biology , organic chemistry
The collapsin response mediator protein 2 (CRMP‐2) is a central molecule regulating axonal growth cone guidance. It interacts with the cytoskeleton and mediates signals related to myelin‐induced axonal growth inhibition. CRMP‐2 has also been characterized as a constituent of neurofibrillary tangles in Alzheimer’s disease. CD spectroscopy and thermal stability assays using the Thermofluor method indicated that Ca 2+ and Mg 2+ affect the stability of CRMP‐2 and prevent the formation of β‐aggregates upon heating. Gel filtration showed that the presence of Ca 2+ or Mg 2+ promoted the formation of CRMP‐2 homotetramers, and this was further proven by small‐angle X‐ray scattering experiments, where a 3D solution structure for CRMP‐2 was obtained. Previously, we described a crystal structure of human CRMP‐2 complexed with calcium. In the present study, we determined the structure of CRMP‐2 in the absence of calcium at 1.9 Å resolution. When Ca 2+ was omitted, crystals could only be grown in the presence of Mg 2+ ions. By a proteomic approach, we further identified a number of post‐translational modifications in CRMP‐2 from rat brain hippocampus and mapped them onto the crystal structure.