title: Crystal structure of the receptor-binding domain from newly emerged Middle East respiratory syndrome coronavirus.
abstract: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 77 people, with a fatality rate of more than 50%. Alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. Here we have identified the receptor-binding domain (RBD) from the MERS-CoV spike protein and determined its crystal structure. This study also presents a structural comparison of MERS-CoV RBD with other coronavirus RBDs, successfully positioning MERS-CoV on the landscape of coronavirus evolution and providing insights into receptor binding by MERS-CoV. Furthermore, we found that MERS-CoV RBD functions as an effective entry inhibitor of MERS-CoV. The identified MERS-CoV RBD may also serve as a potential candidate for MERS-CoV subunit vaccines. Overall, this study enhances our understanding of the evolution of coronavirus RBDs, provides insights into receptor recognition by MERS-CoV, and may help control the transmission of MERS-CoV in humans.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Yaoqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Kanagalaghatta R
authors.initials: KR
authors.lastname: Rajashankar
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Sudhakar S
authors.initials: SS
authors.lastname: Agnihothram
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Yi-Lun
authors.initials: YL
authors.lastname: Lin
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
authors.forename: Fang
authors.initials: F
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D017934:Coronavirus / Q000502:physiology*; D018360:Crystallography, X-Ray; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics; D008877:Middle East; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014764:Viral Proteins; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
references.citation: Nature. 1992 Jun 4;357(6377):417-20
references.pmid: 1350661
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19970-4
references.pmid: 19901337
references.citation: J Virol. 2011 Jun;85(11):5331-7
references.pmid: 21411533
references.citation: J Virol. 2013 Sep;87(17):9939-42
references.pmid: 23824801
references.citation: Virology. 2007 Sep 15;366(1):16-22
references.pmid: 17692355
references.citation: Nature. 2013 Mar 14;495(7440):251-4
references.pmid: 23486063
references.citation: Nucleic Acids Res. 1998 Jan 1;26(1):316-9
references.pmid: 9399863
references.citation: Emerg Infect Dis. 2013 Mar;19(3):456-9
references.pmid: 23622767
references.citation: Virology. 1992 Aug;189(2):792-4
references.pmid: 1322604
references.citation: J Gen Virol. 1986 Jul;67 ( Pt 7):1443-8
references.pmid: 3014054
references.citation: Glycoconj J. 2006 Feb;23(1-2):51-8
references.pmid: 16575522
references.citation: J Immunol. 2005 Apr 15;174(8):4908-15
references.pmid: 15814718
references.citation: Nature. 1992 Jun 4;357(6377):420-2
references.pmid: 1350662
references.citation: N Engl J Med. 2003 May 15;348(20):1953-66
references.pmid: 12690092
references.citation: J Virol. 2013 Jul;87(14):7790-2
references.pmid: 23678167
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Jan;55(Pt 1):247-55
references.pmid: 10089417
references.citation: Nature. 2013 Aug 8;500(7461):227-31
references.pmid: 23831647
references.citation: J Virol. 2008 Jul;82(14):6984-91
references.pmid: 18448527
references.citation: N Engl J Med. 2012 Nov 8;367(19):1814-20
references.pmid: 23075143
references.citation: Nature. 2003 Nov 27;426(6965):450-4
references.pmid: 14647384
references.citation: J Biol Chem. 2006 Jun 9;281(23):15829-36
references.pmid: 16597622
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: J Biol Chem. 2012 Mar 16;287(12):8904-11
references.pmid: 22291007
references.citation: mBio. 2013 Jan 08;4(1):e00548-12
references.pmid: 23300251
references.citation: J Virol. 2012 Mar;86(5):2856-8
references.pmid: 22205743
references.citation: Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5533-6
references.pmid: 1648219
references.citation: Proc Natl Acad Sci U S A. 2005 May 31;102(22):7988-93
references.pmid: 15897467
references.citation: J Virol. 1991 Dec;65(12):6881-91
references.pmid: 1719235
references.citation: mBio. 2013 Apr 30;4(3):e00165-13
references.pmid: 23631916
references.citation: J Virol. 1991 Nov;65(11):6232-7
references.pmid: 1920630
references.citation: Acta Crystallogr D Biol Crystallogr. 2000 Aug;56(Pt 8):965-72
references.pmid: 10944333
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10696-701
references.pmid: 21670291
references.citation: J Virol. 2013 Aug;87(16):9379-83
references.pmid: 23785207
references.citation: J Virol. 2013 Aug;87(15):8638-50
references.pmid: 23720729
references.citation: Nat Rev Microbiol. 2009 Jun;7(6):439-50
references.pmid: 19430490
references.citation: Cell Res. 2013 Aug;23(8):986-93
references.pmid: 23835475
references.citation: J Immunol. 2004 Sep 15;173(6):4050-7
references.pmid: 15356154
references.citation: J Biol Chem. 2012 Dec 7;287(50):41931-8
references.pmid: 23091051
references.citation: Science. 2005 Sep 16;309(5742):1864-8
references.pmid: 16166518
references.citation: J Virol. 2006 May;80(10):4901-8
references.pmid: 16641281
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 Nov;59(Pt 11):1966-73
references.pmid: 14573951
references.citation: Acta Crystallogr D Biol Crystallogr. 2000 Feb;56(Pt 2):232-7
references.pmid: 10666615
references.citation: J Virol. 2006 Jul;80(14):6794-800
references.pmid: 16809285
references.citation: J Virol. 2003 Aug;77(16):8801-11
references.pmid: 12885899
references.citation: Lancet. 2003 Apr 19;361(9366):1319-25
references.pmid: 12711465
references.citation: PLoS Pathog. 2012;8(8):e1002859
references.pmid: 22876187