Intercellular adhesion molecule-3 binding of integrin alphaL beta2 requires both extension and opening of the integrin headpiece.
The leukocyte-restricted integrin alpha(L)beta(2) is required in immune processes such as leukocyte adhesion, migration, and immune synapse formation. Activation of alpha(L)beta(2) by conformational changes promotes alpha(L)beta(2) binding to its ligands, ICAMs. It was reported that different affinity states of alpha(L)beta(2) are required for binding ICAM-1 and ICAM-3. Recently, the bent, extended with a closed headpiece, and extended with open headpiece conformations of alpha(L)beta(2), was reported. To address the overall conformational requirements of alpha(L)beta(2) that allow selective binding of these ICAMs, we examined the adhesion properties of these alpha(L)beta(2) conformers. alpha(L)beta(2) with different conformations were generated by mutations, and verified by using a panel of reporter mAbs that detect alpha(L)beta(2) extension, hybrid domain movement, or I-like domain activation. We report a marked difference between extended alpha(L)beta(2) with closed and open headpieces in their adhesive properties to ICAM-1 and ICAM-3. Our data show that the extension of alpha(L)beta(2) alone is sufficient to mediate ICAM-1 adhesion. By contrast, an extended alpha(L)beta(2) with an open headpiece is required for ICAM-3 adhesion.
Tang
Xiao-Yan
XY
School of Biological Sciences, Nanyang Technological University, Singapore.
Li
Yan-Feng
YF
Tan
Suet-Mien
SM
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D040881:CD11a Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018821:CD18 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
D015703:Antigens, CD; D040881:CD11a Antigen; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human