title: The connection between metal ion affinity and ligand affinity in integrin I domains.
abstract: Integrins are cell-surface heterodimeric proteins that mediate cell-cell, cell-matrix, and cell-pathogen interactions. Half of the known integrin alpha subunits contain inserted domains (I domains) that coordinate ligand through a metal ion. Although the importance of conformational changes within isolated I domains in regulating ligand binding has been reported, the relationship between metal ion binding affinity and ligand binding affinity has not been elucidated. Metal and ligand binding by several I domain mutants that are stabilized in different conformations are investigated using isothermal titration calorimetry and surface plasmon resonance studies. This work suggests an inverse relationship between metal ion affinity and ligand binding affinity (i.e. constructs with a high affinity for ligand exhibit a low affinity for metal). This trend is discussed in the context of structural studies to provide an understanding of interplay between metal ion binding and ligand affinities and conformational changes.
authors: CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
authors: Thomas
authors: T
authors: Vorup-Jensen
authors: Travis T
authors: TT
authors: Waldron
authors: Nathan
authors: N
authors: Astrof
authors: Motomu
authors: M
authors: Shimaoka
authors: Timothy A
authors: TA
authors: Springer
mesh_terms: D019943:Amino Acid Substitution; D002118:Calcium / Q000737:chemistry; D002151:Calorimetry; D002413:Cations, Divalent / Q000737:chemistry*; D016023:Integrins / Q000737:chemistry*; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics; D008274:Magnesium / Q000737:chemistry; D008345:Manganese / Q000737:chemistry; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance
chemical_list: D002413:Cations, Divalent; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1; D008345:Manganese; D008274:Magnesium; D002118:Calcium
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