7dxk

Human 128QHuntingtin-HAP40 complex structureHuman 128QHuntingtin-HAP40 complex structure

Structural highlights 7dxk is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.1Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease HAP40_HUMAN Up-regulated in brain tissue from patients affected by Huntington's disease (at protein level) (PubMed:16476778). In a Huntington's disease mouse model overexpression of F8A1/F8A2/F8A3 impairs proteasome activity leading to the accumulation of mutant HTT and causes defective mitochondrial functions (PubMed:27815841, PubMed:29209146). Function HAP40_HUMAN RAB5A effector molecule that is involved in vesicular trafficking of early endosomes (PubMed:16476778). Mediates the recruitment of HTT by RAB5A onto early endosomes. The HTT-F8A1/F8A2/F8A3-RAB5A complex stimulates early endosomal interaction with actin filaments and inhibits interaction with microtubules, leading to the reduction of endosome motility (PubMed:16476778). Publication Abstract from PubMed The abnormal amplification of a CAG repeat in the gene coding for huntingtin (HTT) leads to Huntington's disease (HD). At the protein level, this translates into the expansion of a polyglutamine (polyQ) stretch located at the HTT N terminus, which renders HTT aggregation prone by unknown mechanisms. Here we investigated the effects of polyQ expansion on HTT in a complex with its stabilizing interaction partner huntingtin-associated protein 40 (HAP40). Surprisingly, our comprehensive biophysical, crosslinking mass spectrometry and cryo-EM experiments revealed no major differences in the conformation of HTT-HAP40 complexes of various polyQ length, including 17QHTT-HAP40 (wild type), 46QHTT-HAP40 (typical polyQ length in HD patients), and 128QHTT-HAP40 (extreme polyQ length). Thus, HTT polyQ expansion does not alter the global conformation of HTT when associated with HAP40. Pathological polyQ expansion does not alter the conformation of the Huntingtin-HAP40 complex.,Huang B, Guo Q, Niedermeier ML, Cheng J, Engler T, Maurer M, Pautsch A, Baumeister W, Stengel F, Kochanek S, Fernandez-Busnadiego R Structure. 2021 Aug 5;29(8):804-809.e5. doi: 10.1016/j.str.2021.04.003. Epub 2021 , Apr 27. PMID:33909994 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Huntingtin

spinqualitylabelsall models 7dxk, resolution 4.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image