Structure of the N-terminal domain of human CEACAM1: binding target of the opacity proteins during invasion of Neisseria meningitidis and N. gonorrhoeae.
CEACAM1 is a cellular adhesion molecule whose protein expression is down-regulated in several carcinomas and which also contributes to the pathogenicity of Neisseria by acting as a receptor for Opa proteins. The crystal structure of the N-terminal (D1) domain of human CEACAM1 has been determined at 2.2 Angstrom resolution. The structure shows several differences compared with a lower resolution model of the same domain from mouse solved previously, especially in the functional regions. Mapping of the sites of mutations that lower or abolish the binding of CEACAM1 to Opa proteins shows a distinct clustering of residues on the GFCC'C'' face of the molecule. Prominent amongst these are residues in the C, C' and F strands and the CC' loop. A similar analysis shows that the region responsible for homophilic or heterophilic interactions of CEACAM1 is also on the GFCC'C'' face and overlaps partially with the Opa-binding region. This higher resolution structure of CEACAM1 will facilitate a more precise dissection of its functional regions in the context of neisserial pathogenesis, cellular adhesion and immune evasion.
Fedarovich
Alena
A
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Tomberg
Joshua
J
Nicholas
Robert A
RA
Davies
Christopher
C
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry* / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000502:physiology; D018360:Crystallography, X-Ray; D006069:Gonorrhea / Q000378:metabolism; D006801:Humans; D008589:Meningococcal Infections / Q000378:metabolism; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C090348:Opa protein, Neisseria