Shape and shift changes related to the function of leukocyte integrins LFA-1 and Mac-1.
Integrin activity on leukocytes is controlled tightly, ensuring that ligand binding occurs only when leukocytes are in contact with their targets. For an integrinlike LFA-1, this ligand-binding activity comes about as a result of increased integrin clustering. Affinity regulation of integrins also plays a role, but the conformational changes giving rise to increased affinity appear to be secondary to clustering. Conformationally altered LFA-1 can be created artificially by deletion of the I domain, which is the key domain involved in ligand binding for many but not all integrins. Although I domain-deleted LFA-1 (DeltaI-LFA-1) cannot bind ligand, it is able to signal constitutively into the cell. One measure of this signaling activity is the ability of DeltaI-LFA-1 to activate beta1 integrins on the same T lymphocyte. Leukocytes use LFA-1 to migrate across the endothelium. Active beta1 integrins may be required subsequently to bind the matrix proteins encountered by leukocytes as they continue their voyage into the tissue interior.
Hogg
N
N
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, London, England, UK. hogg@icrf.icnet.uk
Leitinger
B
B
D020816:Amino Acid Motifs; D002413:Cations, Divalent / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D016023:Integrins / Q000737:chemistry / Q000502:physiology*; D007962:Leukocytes / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000502:physiology*; D046911:Macromolecular Substances; D016177:Macrophage-1 Antigen / Q000737:chemistry / Q000502:physiology*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
D002413:Cations, Divalent; D019012:Integrin beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D046911:Macromolecular Substances; D016177:Macrophage-1 Antigen