3u2i

X-ray crystal structure of human Transthyretin at room temperature

spinqualitylabelsall models 3u2i, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3u2i 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 1.7Å 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) is a tetrameric protein associated with human amyloidosis. In vitro, the formation of amyloid fibrils by TTR is known to be promoted by low pH. Here we show the neutron structure of TTR, focusing on the hydrogen bonds, protonation states and pH sensitivities. A large crystal was prepared at pD 7.4 for neutron protein crystallography. Neutron diffraction studies were conducted using the IBARAKI Biological Crystal Diffractometer with the time-of-flight method. The neutron structure solved at 2.0A resolution revealed the protonation states of His88 and the detailed hydrogen-bond network depending on the protonation states of His88. This hydrogen-bond network is composed of Thr75, Trp79, His88, Ser112, Pro113, Thr118-B and four water molecules, and is involved in both monomer-monomer and dimer-dimer interactions, suggesting that the double protonation of His88 by acidification breaks the hydrogen-bond network and causes the destabilization of the TTR tetramer. In addition, the comparison with X-ray structure at pH 4.0 indicated that the protonation occurred to Asp74, His88 and Glu89 at pH 4.0. Our neutron model provides insights into the molecular stability of TTR related to the hydrogen-bond network, the pH sensitivity and the CH...O weak hydrogen bond. Hydrogen-bond network and pH sensitivity in transthyretin: Neutron crystal structure of human transthyretin.,Yokoyama T, Mizuguchi M, Nabeshima Y, Kusaka K, Yamada T, Hosoya T, Ohhara T, Kurihara K, Tomoyori K, Tanaka I, Niimura N J Struct Biol. 2012 Feb;177(2):283-90. Epub 2012 Jan 11. PMID:22248451 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transthyretin 3D structures

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