6jvb | pdb_00006jvb
Crystal Structure of Human CRMP2 1-532, AGE-modified
Structural highlights
Function[DPYL2_HUMAN] Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton (By similarity). Plays a role in neuron projection morphogenesis.[1] [2] Publication Abstract from PubMedEnhanced carbonyl stress underlies a subset of schizophrenia, but its causal effects remain elusive. Here, we elucidated the molecular mechanism underlying the effects of carbonyl stress in iPS cells in which the gene encoding zinc metalloenzyme glyoxalase I (GLO1), a crucial enzyme for the clearance of carbonyl stress, was disrupted. The iPS cells exhibited significant cellular and developmental deficits, and hyper-carbonylation of collapsing response mediator protein 2 (CRMP2). Structural and biochemical analyses revealed an array of multiple carbonylation sites in the functional motifs of CRMP2, particularly D-hook (for dimerization) and T-site (for tetramerization), which are critical for the activity of the CRMP2 tetramer. Interestingly, carbonylated CRMP2 was stacked in the multimer conformation by irreversible cross-linking, resulting in loss of its unique function to bundle microtubules. Thus, the present study revealed that the enhanced carbonyl stress stemmed from the genetic aberrations results in neurodevelopmental deficits through the formation of irreversible dysfunctional multimer of carbonylated CRMP2. Enhanced carbonyl stress induces irreversible multimerization of CRMP2 in schizophrenia pathogenesis.,Toyoshima M, Jiang X, Ogawa T, Ohnishi T, Yoshihara S, Balan S, Yoshikawa T, Hirokawa N Life Sci Alliance. 2019 Oct 7;2(5). pii: 2/5/e201900478. doi:, 10.26508/lsa.201900478. Print 2019 Oct. PMID:31591136[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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