5n7c

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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN]] Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.<ref>PMID:3714052</ref>
[[http://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN]] Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.<ref>PMID:3714052</ref>
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== Publication Abstract from PubMed ==
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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.
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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<ref>PMID:30213975</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
== References ==
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<references/>

Revision as of 08:33, 26 September 2018

Human TTR altered conformation from soaking in CuCl2.

5n7c, resolution 2.45Å

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