5n5q

Human TTR altered conformation from soaking in iron chloride.

spinqualitylabelsall models 5n5q, resolution 2.53Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5n5q is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.53Å Ligands: ACT, FE, FFE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TTHY_HUMAN Defects in TTR are the cause of amyloidosis transthyretin-related (AMYL-TTR) [MIM:105210. A hereditary generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment (oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor deterioration, variable amyloid deposition in the vitreous humor. Defects in TTR are a cause of hyperthyroxinemia dystransthyretinemic euthyroidal (HTDE) [MIM:145680. It is a condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities. Defects in TTR are a cause of carpal tunnel syndrome type 1 (CTS1) [MIM:115430. It is a condition characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis. Function TTHY_HUMAN Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain. Publication Abstract from PubMed Transthyretin (TTR), a homotetrameric protein that transports thyroxine and retinol both in plasma and in cerebrospinal (CSF) fluid provides a natural protective response against Alzheimer's disease (AD), modulates amyloid-beta (Abeta) deposition by direct interaction and co-localizes with Abeta in plaques. TTR levels are lower in the CSF of AD patients. Zn(2+), Mn(2+) and Fe(2+) transform TTR into a protease able to cleave Abeta. To explain these activities, monomer dissociation or conformational changes have been suggested. Here, we report that when TTR crystals are exposed to copper or iron salts, the tetramer undergoes a significant conformational change that alters the dimer-dimer interface and rearranges residues implicated in TTR's ability to neutralize Abeta. We also describe the conformational changes in TTR upon the binding of the various metal ions. Furthermore, using bio-layer interferometry (BLI) with immobilized Abeta(1-28), we observe the binding of TTR only in the presence of copper. Such Cu(2+)-dependent binding suggests a recognition mechanism whereby Cu(2+) modulates both the TTR conformation, induces a complementary Abeta structure and may participate in the interaction. Cu(2+)-soaked TTR crystals show a conformation different from that induced by Fe(2+), and intriguingly, TTR crystals grown in presence of Abeta(1-28) show different positions for the copper sites from those grown its absence. Copper mediated amyloid-beta binding to Transthyretin.,Ciccone L, Fruchart-Gaillard C, Mourier G, Savko M, Nencetti S, Orlandini E, Servent D, Stura EA, Shepard W Sci Rep. 2018 Sep 13;8(1):13744. doi: 10.1038/s41598-018-31808-5. PMID:30213975 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transthyretin 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA