6r4r
From Proteopedia
Cryo-EM Structure of the PI3-Kinase SH3 Domain Amyloid Fibril
Structural highlights
Function[P85A_BOVIN] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity). Publication Abstract from PubMedHigh resolution structural information on amyloid fibrils is crucial for the understanding of their formation mechanisms and for the rational design of amyloid inhibitors in the context of protein misfolding diseases. The Src-homology 3 domain of phosphatidyl-inositol-3-kinase (PI3K-SH3) is a model amyloid system that plays a pivotal role in our basic understanding of protein misfolding and aggregation. Here, we present the atomic model of the PI3K-SH3 amyloid fibril with a resolution determined to 3.4 A by cryo-electron microscopy (cryo-EM). The fibril is composed of two intertwined protofilaments that create an interface spanning 13 residues from each monomer. The model comprises residues 1-77 out of 86 amino acids in total, with the missing residues located in the highly flexible C-terminus. The fibril structure allows us to rationalise the effects of chemically conservative point mutations as well as of the previously reported sequence perturbations on PI3K-SH3 fibril formation and growth. Atomic structure of PI3-kinase SH3 amyloid fibrils by cryo-electron microscopy.,Roder C, Vettore N, Mangels LN, Gremer L, Ravelli RBG, Willbold D, Hoyer W, Buell AK, Schroder GF Nat Commun. 2019 Aug 21;10(1):3754. doi: 10.1038/s41467-019-11320-8. PMID:31434882[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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