Biomaterial Database

Differential ligand binding specificities of recombinant CD11b/CD18 integrin I-domain. 1994

L Zhou, and D H Lee, and J Plescia, and C Y Lau, and D C Altieri

R. W. Johnson Pharmaceutical Research Institute, Don Mills, Ontario, Canada.

The alpha subunits of leukocyte CD11/CD18 integrins contain an approximately 200-amino acid "inserted" domain (I-domain) that may be important for multivalent adhesive recognitions. A recombinant form of the I-domain of CD11b/CD18 was generated and analyzed directly for interaction with complementary integrin ligands. CD11b I-domain bound the activation-dependent monoclonal antibody 7E3, and the functionally blocking anti-CD11b monoclonal antibodies OKM9, 60.1, and LM2/1, but not OKM1 or M1/70. Fibrinogen or soluble intercellular adhesion molecule-1 associated with CD11b I-domain in a concentration-dependent manner. Binding of 125I-fibrinogen to recombinant CD11b I-domain was saturable, governed by a Kd of approximately 0.22 +/- 0.06 microM, and fully inhibited by molar excess of unlabeled fibrinogen, or by the P1 peptide (KY)GWTVFQKRLDGSV (IC50 approximately 2.5-5 microM), duplicating the fibrinogen gamma chain sequence Gly190-Val202. In contrast, 125I-factor X binding to CD11b I-domain was only partially inhibited (50-60%) by a molar excess of unlabeled factor X, and entirely unaffected by functionally blocking anti-CD11b monoclonal antibodies or by factor X-derived synthetic peptidyl antagonists. We conclude that the I-domain of CD11b participates in qualitative mechanisms of receptor activation and contains the binding site(s) for the CD11b/CD18 ligands fibrinogen and intercellular adhesion molecule-1, while it is only minimally implicated in the recognition of factor X.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D005170	Factor X	Storage-stable glycoprotein blood coagulation factor that can be activated to factor Xa by both the intrinsic and extrinsic pathways. A deficiency of factor X, sometimes called Stuart-Prower factor deficiency, may lead to a systemic coagulation disorder.	Autoprothrombin III,Coagulation Factor X,Stuart Factor,Stuart-Prower Factor,Blood Coagulation Factor X,Factor 10,Factor Ten,Stuart Prower Factor,Factor X, Coagulation
D005340	Fibrinogen	Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.	Coagulation Factor I,Factor I,Blood Coagulation Factor I,gamma-Fibrinogen,Factor I, Coagulation,gamma Fibrinogen
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000939	Epitopes	Sites on an antigen that interact with specific antibodies.	Antigenic Determinant,Antigenic Determinants,Antigenic Specificity,Epitope,Determinant, Antigenic,Determinants, Antigenic,Specificity, Antigenic