Intermediate monomer-dimer equilibrium structure of native ICAM-1: implication for enhanced cell adhesion.
Dimeric intercellular adhesion molecule-1 (ICAM-1) has been known to more efficiently mediate cell adhesion than monomeric ICAM-1. Here, we found that truncation of the intracellular domain of ICAM-1 significantly enhances surface dimerization based on the two criteria: 1) the binding degree of monomer-specific antibody CA-7 and 2) the ratio of dimer/monomer when a mutation (L42→C42) was introduced in the interface of domain 1. Mutation analysis revealed that the positively charged amino acids, including very membrane-proximal ⁵⁰⁵R, are essential for maintaining the structural transition between the monomer and dimer. Despite a strong dimer presentation, the ICAM-1 mutants lacking an intracellular domain (IC1ΔCTD) or containing R to A substitution in position 505 (⁵⁰⁵R/A) supported a lower degree of cell adhesion than did wild-type ICAM-1. Collectively, these results demonstrate that the native structure of surface ICAM-1 is not a dimer, but is an intermediate monomer-dimer equilibrium structure by which the effectiveness of ICAM-1 can be fully achieved.
School of Life Sciences, and Immune Synapse Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
Hyun-Mee
HM
Oh
Min-Sung
MS
Kwon
Hyang-Jin
HJ
Kim
Byeong-Hun
BH
Jeon
Hye-Ran
HR
Kim
Hyang-Ok
HO
Choi
Bo-Ra
BR
Na
Soo-Hyun
SH
Eom
Nam Woong
NW
Song
Chang-Duk
CD
Jun
D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary; D019281:Dimerization; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D007668:Kidney / Q000166:cytology; D046911:Macromolecular Substances / Q000378:metabolism; D008961:Models, Structural; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology
D018076:DNA, Complementary; D046911:Macromolecular Substances; D034741:RNA, Small Interfering; D018799:Intercellular Adhesion Molecule-1