Structure and binding interface of the cytosolic tails of alphaXbeta2 integrin.
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Chua GL, Tang XY, Patra AT, Tan SM, Bhattacharjya S
Structure and binding interface of the cytosolic tails of alphaXbeta2 integrin.
PLoS One. 2012;7(7):e41924. doi: 10.1371/journal.pone.0041924. Epub 2012 Jul 26.
- PubMed ID
- 22844534 [ View in PubMed]
- 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, alpha and beta. In humans, 18 alpha and 8 beta 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. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we have investigated structure and interactions of CTs of the leukocyte specific integrin alphaXbeta2. We determined the atomic resolution structure of a myristoylated CT of alphaX in perdeuterated dodecylphosphocholine (DPC) by NMR spectroscopy. Our results reveal that the 35-residue long CT of alphaX adopts an alpha-helical conformation for residues F4-N17 at the N-terminal region. The remaining residues located at the C-terminal segment of alphaX 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 alphaX CT. Interactions between alphaX and beta2 CTs are demonstrated by (15)N-(1)H HSQC NMR experiments. We find that residues constituting the polar face of the helical conformation of alphaX are involved in interactions with the N-terminal residues of beta2 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/SIGNIFICANCE: The current study provides important insights into the conservation of interactions and structures among different CTs of integrins.