5lg8
From Proteopedia
Human L-type ferritin iron loaded for 60 minutes
Structural highlights
DiseaseFRIL_HUMAN Defects in FTL are the cause of hereditary hyperferritinemia-cataract syndrome (HHCS) [MIM:600886. It is an autosomal dominant disease characterized by early-onset bilateral cataract. Affected patients have elevated level of circulating ferritin. HHCS is caused by mutations in the iron responsive element (IRE) of the FTL gene.[1] Defects in FTL are the cause of neurodegeneration with brain iron accumulation type 3 (NBIA3) [MIM:606159; also known as adult-onset basal ganglia disease. It is a movement disorder with heterogeneous presentations starting in the fourth to sixth decade. It is characterized by a variety of neurological signs including parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit and episodic psychosis. It is linked with decreased serum ferritin levels.[2] [3] FunctionFRIL_HUMAN Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).[4] [5] Publication Abstract from PubMedX-ray structures of homopolymeric L-ferritin obtained by freezing protein crystals at increasing exposure times to a ferrous solution showed the progressive formation of a triiron cluster on the inner cage surface of each subunit. After 60 min exposure, a fully assembled (mu3-oxo)Tris[(mu2-peroxo)(mu2-glutamato-kappaO:kappaO')](glutamato-kappaO)(diaqu o)triiron(III) anionic cluster appears in human L-ferritin. Glu60, Glu61, and Glu64 provide the anchoring of the cluster to the protein cage. Glu57 shuttles incoming iron ions toward the cluster. We observed a similar metallocluster in horse spleen L-ferritin, indicating that it represents a common feature of mammalian L-ferritins. The structures suggest a mechanism for iron mineral formation at the protein interface. The functional significance of the observed patch of carboxylate side chains and resulting metallocluster for biomineralization emerges from the lower iron oxidation rate measured in the E60AE61AE64A variant of human L-ferritin, leading to the proposal that the observed metallocluster corresponds to the suggested, but yet unobserved, nucleation site of L-ferritin. Chemistry at the protein-mineral interface in L-ferritin assists the assembly of a functional (mu3-oxo)Tris[(mu2-peroxo)] triiron(III) cluster.,Pozzi C, Ciambellotti S, Bernacchioni C, Di Pisa F, Mangani S, Turano P Proc Natl Acad Sci U S A. 2017 Feb 15. pii: 201614302. doi:, 10.1073/pnas.1614302114. PMID:28202724[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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