Structural basis for mammalian vitamin B12 transport by transcobalamin

Proceedings of the National Academy of Sciences of the United States of America
Jochen WuergesLucio Randaccio

Abstract

Cobalamin (Cbl, vitamin B(12)) serves for two essential cofactors in mammals. The pathway for its intestinal absorption, plasma transport, and cellular uptake uses cell surface receptors and three Cbl-transporting proteins, haptocorrin, intrinsic factor, and transcobalamin (TC). We present the structure determination of a member of the mammalian Cbl-transporter family. The crystal structures of recombinant human and bovine holo-TCs reveal a two-domain architecture, with an N-terminal alpha(6)-alpha(6) barrel and a smaller C-terminal domain. One Cbl molecule in base-on conformation is buried inside the domain interface. Structural data combined with previous binding assays indicate a domain motion in the first step of Cbl binding. In a second step, the weakly coordinated ligand H(2)O at the upper axial side of added H(2)O-Cbl is displaced by a histidine residue of the alpha(6)-alpha(6) barrel. Analysis of amino acid conservation on TC's surface in orthologous proteins suggests the location of the TC-receptor-recognition site in an extended region on the alpha(6)-alpha(6) barrel. The TC structure allows for the mapping of sites of amino acid variation due to polymorphisms of the human TC gene. Structural information is used to pr...Continue Reading

References

Nov 1, 1979·The Journal of Clinical Investigation·F I HauraniR Rubin
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Nov 20, 1980·The New England Journal of Medicine·P A SeligmanR H Allen
Aug 2, 1996·Science·L Holm, C Sander
Sep 20, 1997·Science·K U WendtG E Schulz
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
May 20, 1999·Nature Structural Biology·A PerrakisV S Lamzin
Sep 3, 1999·The Journal of Biological Chemistry·S N FedosovT E Petersen
Sep 28, 1999·The Journal of Nutrition·B SeetharamN Li
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Sep 22, 2001·Acta Crystallographica. Section D, Biological Crystallography·J Navaza
Nov 22, 2001·Acta Crystallographica. Section D, Biological Crystallography·G GarauL Randaccio
Jan 15, 2002·The Journal of Biological Chemistry·Sergey N FedosovTorben E Petersen
Sep 28, 2002·Acta Crystallographica. Section D, Biological Crystallography·Thomas R Schneider, George M Sheldrick
Nov 26, 2002·BMJ : British Medical Journal·David S WaldJoan K Morris
Dec 12, 2002·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth L BorthsDouglas C Rees
Mar 13, 2003·Kidney International·Marc R Hammerman
Mar 28, 2003·American Journal of Physiology. Cell Physiology·Seema KalraBellur Seetharam
Apr 16, 2003·Kidney International. Supplement·Gere Sunder-Plassmann, Manuela Födinger
Jul 5, 2003·The Journal of Surgical Research·James M McGreevyCharles B Grissom
Oct 7, 2003·Annual Review of Biochemistry·Ruma Banerjee, Stephen W Ragsdale
Oct 24, 2003·Acta Crystallographica. Section D, Biological Crystallography·G BricogneW Paciorek
Nov 25, 2003·Clinical Chemistry·Zouë Lloyd-WrightEbba Nexø
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Oct 2, 2004·Journal of Inorganic Biochemistry·Gregory Russell-JonesDavid Nowotnik
Oct 19, 2004·Archives of Biochemistry and Biophysics·Seema KalraBellur Seetharam
Nov 13, 2004·Preventive Medicine·Maike WoltersAndreas Hahn
Jan 18, 2005·Biochemical and Biophysical Research Communications·Edward V QuadrosJeffrey M Sequeira
Mar 23, 2005·Birth Defects Research. Part A, Clinical and Molecular Teratology·Deborah A SwansonLawrence C Brody
Jun 9, 2005·The American Journal of Clinical Nutrition·Kristina M von Castel-DunwoodyLynn B Bailey
Jul 28, 2005·The FEBS Journal·Sergey N FedosovTorben E Petersen
Apr 13, 2006·Journal of Synchrotron Radiation·F ChamployC Kratky
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Oct 29, 2008·Journal of Inherited Metabolic Disease·C PrasadC A Rupar
Mar 31, 2010·Journal of Inherited Metabolic Disease·Manuel SchiffStéphane Giraudier
Jul 17, 2012·The British Journal of Nutrition·Marcella MartinelliRossella Solmi
Aug 10, 2013·Journal of Medicinal Chemistry·Fabio ZobiAnna Yu Bogdanova
Jul 9, 2011·The Journal of Organic Chemistry·Keith ó ProinsiasDorota Gryko
Apr 3, 2013·The Journal of Organic Chemistry·Sylwester KurcońDorota Gryko
Sep 3, 2010·European Journal of Clinical Nutrition·A Stanisławska-SachadynA S Whitehead
Mar 11, 2010·European Journal of Clinical Nutrition·M G GarrodJ W Miller
Jul 5, 2008·Nature Protocols·Gerrit LangerAnastassis Perrakis
May 2, 2012·Nature Reviews. Gastroenterology & Hepatology·Marianne J NielsenSøren K Moestrup
Aug 8, 2008·Chemical Communications : Chem Comm·Riya MukherjeeNicola E Brasch
Mar 12, 2008·Proceedings of the National Academy of Sciences of the United States of America·Supratim DattaRowena G Matthews
Dec 5, 2009·Proceedings of the National Academy of Sciences of the United States of America·Shyue-fang Battaglia-HsuJean-Louis Guéant
Jun 4, 2011·Acta Crystallographica. Section D, Biological Crystallography·Gerwald JoglPaul Langan
Dec 12, 2012·Advanced Drug Delivery Reviews·Taslim A Al-HilalYoungro Byun
Oct 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·F S MathewsN Sukumar
Dec 7, 2010·Expert Opinion on Drug Delivery·Susan M ClardyRobert P Doyle
Dec 24, 2015·Bioconjugate Chemistry·Aleksandra WierzbaDorota Gryko
Feb 11, 2010·Clinical Biochemistry·Rita CastroIsabel Tavares de Almeida
Mar 31, 2009·Free Radical Biology & Medicine·J Brice WeinbergDipak K Ghosh
Mar 5, 2008·Molecular Microbiology·Mari Cruz Pérez-MarínMontserrat Elías-Arnanz
Oct 17, 2009·British Journal of Haematology·Edward V Quadros
Mar 10, 2016·European Journal of Clinical Investigation·Agata Sobczyńska-MaleforaLawrence C Brody
Dec 6, 2011·Current Opinion in Biotechnology·Steven M YannoneJohn A Tainer
Aug 12, 2009·Current Opinion in Chemical Biology·Ruma BanerjeeDominique Padovani
Mar 16, 2017·Acta Crystallographica. Section D, Structural Biology·Heping ZhengWladek Minor
Jan 8, 2016·Metallomics : Integrated Biometal Science·Mai Thanh Quynh TranRoger Alberto
Aug 20, 2015·Chemical Communications : Chem Comm·Felix Zelder
Sep 15, 2017·PloS One·Joël S BlochKaspar P Locher

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