7roj
From Proteopedia
Amyloid-related segment of alphaB-crystallin residues 90-100 with G95W mutation
Structural highlights
Disease[CRYAB_HUMAN] Posterior polar cataract;Alpha-crystallinopathy;Zonular cataract;Familial isolated dilated cardiomyopathy;Fatal infantile hypertonic myofibrillar myopathy. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function[CRYAB_HUMAN] May contribute to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions. Publication Abstract from PubMedAtomic structures of amyloid oligomers that capture the neurodegenerative disease pathology are essential to understand disease-state causes and finding cures. Here we investigate the G6W mutation of the cytotoxic, hexameric amyloid model KV11. The mutation results into an asymmetric dodecamer composed of a pair of 30 degrees twisted antiparallel beta-sheets. The complete break between adjacent beta-strands is unprecedented among amyloid fibril crystal structures and supports that our structure is an oligomer. The poor shape complementarity between mated sheets reveals an interior channel for binding lipids, suggesting that the toxicity may be due to a perturbation of lipid transport rather than a direct disruption of membrane integrity. Viability assays on mouse suprachiasmatic nucleus, anterior hypothalamus, and cerebral cortex demonstrated selective regional vulnerability consistent with Alzheimer's disease. Neuropeptides released from the brain slices may provide clues to how G6W initiates cellular injury. Atomic view of an amyloid dodecamer exhibiting selective cellular toxic vulnerability in acute brain slices.,Gray ALH, Sawaya MR, Acharyya D, Lou J, Edington EM, Best MD, Prosser RA, Eisenberg DS, Do TD Protein Sci. 2021 Dec 26. doi: 10.1002/pro.4268. PMID:34954854[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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