Identification and comparison of residues critical for cell-adhesion activities of two neutrophil CD66 antigens, CEACAM6 and CEACAM8.
CEACAM6 (CD66c) and CEACAM8 (CD66b) are cell-adhesion proteins on neutrophils that belong to the human carcinoembryonic antigen (CEA) family. CEACAM6 reveals homophilic adhesion and heterophilic adhesion to other CEACAM family antigens including CEACAM8, CEACAM1, and CEA, whereas CEACAM8 exhibits only heterophilic adhesion to CEACAM6. Here, we investigated and compared structural requirements for the homophilic adhesion of CEACAM6 and heterophilic adhesion between CEACAM6 and CEACAM8 at the amino acid level by using CHO transfectants expressing their mutant and chimeric proteins. The NH(2)-terminal domain (N-domain) of CEACAM6 expressed on a CHO cell was suggested to bind the N-domain of CEACAM6 or CEACAM8 on the opposing cell. By homologue-scanning mutagenesis, we found that the locations of the sequences critical for the adhesion of CEACAM6 to itself and to CEACAM8 are overlapped and that they are highly similar but not identical to the locations of the residues previously shown to be essential for the binding of CEACAM antigens to Opa proteins of pathogenic NEISSERIAE: Our findings imply that subtle differences in the N-domain sequences determine the specificity of the CEACAM antigens on neutrophils for interaction with the same or different CEACAM antigens and the bacterial proteins.
Kuroki
M
M
Department of Biochemistry, School of Medicine, Fukuoka University, Fukuoka, Japan. mokuroki@fukuoka-u.ac.jp
Abe
H
H
Imakiirei
T
T
Liao
S
S
Uchida
H
H
Yamauchi
Y
Y
Oikawa
S
S
Kuroki
M
M
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D006224:Cricetinae; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009504:Neutrophils / Q000276:immunology*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014162:Transfection
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C504117:CEACAM6 protein, human; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins