Calcium and hydroxyapatite binding site of human vitronectin provides insights to abnormal deposit formation.

Proceedings of the National Academy of Sciences of the United States of America
Kyungsoo ShinFrancesca M Marassi

Abstract

The human blood protein vitronectin (Vn) is a major component of the abnormal deposits associated with age-related macular degeneration, Alzheimer's disease, and many other age-related disorders. Its accumulation with lipids and hydroxyapatite (HAP) has been demonstrated, but the precise mechanism for deposit formation remains unknown. Using a combination of solution and solid-state NMR experiments, cosedimentation assays, differential scanning fluorimetry (DSF), and binding energy calculations, we demonstrate that Vn is capable of binding both soluble ionic calcium and crystalline HAP, with high affinity and chemical specificity. Calcium ions bind preferentially at an external site, at the top of the hemopexin-like (HX) domain, with a group of four Asp carboxylate groups. The same external site is also implicated in HAP binding. Moreover, Vn acquires thermal stability upon association with either calcium ions or crystalline HAP. The data point to a mechanism whereby Vn plays an active role in orchestrating calcified deposit formation. They provide a platform for understanding the pathogenesis of macular degeneration and other related degenerative disorders, and the normal functions of Vn, especially those related to bone resor...Continue Reading

References

Sep 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R PytelaE Ruoslahti
Apr 1, 1988·Cell Structure and Function·K KubotaM Hayashi
Jul 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·E G HaymanE Ruoslahti
Apr 1, 1981·The Journal of General Physiology·S McLaughlinA McLaughlin
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·F M MarassiS J Opella
Mar 4, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G S HagemanD H Anderson
Jan 5, 2000·Journal of Magnetic Resonance·B M FungK Ermolaev
Jul 20, 2002·Journal of Molecular Biology·Hyunju ChaHans Brandstetter
Sep 11, 2002·Angewandte Chemie·Sergey V Dorozhkin, Matthias Epple
Jun 17, 2003·Nature Structural Biology·Aiwu ZhouRandy J Read
Oct 31, 2003·Nature·Quyen Q HoangDaniel S C Yang
Oct 11, 2005·Protein Expression and Purification·Justyna MysliwyJoachim Grötzinger
Jan 6, 2006·Magnetic Resonance in Chemistry : MRC·Christian JägerMatthias Epple
Dec 23, 2006·Journal of Leukocyte Biology·Helene PiccardGhislain Opdenakker
Mar 3, 2007·The Journal of Clinical Investigation·Tomas VaisarJay W Heinecke
Mar 21, 2008·Journal of Computational Chemistry·Sunhwan JoWonpil Im
May 30, 2008·Nucleic Acids Research·Sunhwan JoWonpil Im
Sep 20, 2008·Chemical Reviews·Adele L Boskey, Rani Roy
Oct 23, 2008·Molecular Neurodegeneration·Thuzar M ShinJeannie Chen
May 16, 2009·Journal of Computational Chemistry·B R BrooksM Karplus
Nov 7, 2009·Methods in Enzymology·Larry J CummingsKimberly Brisack
Sep 3, 2010·Molecular Microbiology·Birendra SinghKristian Riesbeck
Nov 16, 2010·Nature Materials·Archan DeyNico A J M Sommerdijk
Dec 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Y-Y HuK Schmidt-Rohr
Jun 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ivano BertiniPaola Turano
Aug 2, 2011·Seminars in Thrombosis and Hemostasis·Klaus T Preissner, Ute Reuning
Oct 5, 2011·Proceedings of the National Academy of Sciences of the United States of America·Lincoln V JohnsonDon H Anderson
Dec 17, 2011·Annals of the New York Academy of Sciences·T J Chambers, K Fuller
Jan 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Richard B ThompsonImre Lengyel
Sep 18, 2015·Microbiology·Sara Schesser BartraGregory V Plano
Jul 28, 2016·The Journal of Biological Chemistry·Ernesto Carafoli, Joachim Krebs
Mar 16, 2017·Acta Crystallographica. Section D, Structural Biology·Heping ZhengWladek Minor
May 17, 2017·Biophysics Reviews·Ashit Rao, Helmut Cölfen
Apr 6, 2018·Ophthalmic Research·Lajos CsincsikImre Lengyel
Oct 26, 2018·Investigative Ophthalmology & Visual Science·Christine A Curcio
Nov 9, 2018·Science Translational Medicine·Anna C S TanChristine A Curcio
Dec 21, 2018·Progress in Retinal and Eye Research·Arthur A BergenImre Lengyel

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