title: Structure and binding interface of the cytosolic tails of αXβ2 integrin.
abstract: BACKGROUND
  Integrins are signal transducer proteins involved in a number of vital physiological processes including cell adhesion, proliferation and migration. Integrin molecules are hetero-dimers composed of two distinct subunits, α and β. In humans, 18 α and 8 β subunits are combined into 24 different integrin molecules. Each of the subunit comprises a large extracellular domain, a single pass transmembrane segment and a cytosolic tail (CT). The CTs of integrins are vital for bidirectional signal transduction and in maintaining the resting state of the receptors. A large number of intracellular proteins have been found to interact with the CTs of integrins linking integrins to the cytoskeleton.
  
  
  RESULTS
  In this work, we have investigated structure and interactions of CTs of the leukocyte specific integrin αXβ2. We determined the atomic resolution structure of a myristoylated CT of αX in perdeuterated dodecylphosphocholine (DPC) by NMR spectroscopy. Our results reveal that the 35-residue long CT of αX adopts an α-helical conformation for residues F4-N17 at the N-terminal region. The remaining residues located at the C-terminal segment of αX delineate a long loop of irregular conformations. A segment of the loop maintains packing interactions with the helical structure by an extended non-polar surface of the αX CT. Interactions between αX and β2 CTs are demonstrated by (15)N-(1)H HSQC NMR experiments. We find that residues constituting the polar face of the helical conformation of αX are involved in interactions with the N-terminal residues of β2 CT. A docked structure of the CT complex indicates that a network of polar and/or salt-bridge interactions may sustain the heteromeric interactions.
  
  
  CONCLUSIONS
  The current study provides important insights into the conservation of interactions and structures among different CTs of integrins.
authors: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors: Geok-Lin
authors: GL
authors: Chua
authors: Xiao-Yan
authors: XY
authors: Tang
authors: Alok Tanala
authors: AT
authors: Patra
authors: Suet-Mien
authors: SM
authors: Tan
authors: Surajit
authors: S
authors: Bhattacharjya
mesh_terms: D000595:Amino Acid Sequence; D003600:Cytosol / Q000378:metabolism*; D016167:Integrin alphaXbeta2 / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019814:Myristic Acid / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D046188:Protein Modification, Translational; D017434:Protein Structure, Tertiary
chemical_list: D016167:Integrin alphaXbeta2; D019814:Myristic Acid