Structure and Binding Interface of the Cytosolic Tails of αXβ2 Integrin

<div><h3>Background</h3><p>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.</p> <h3>Methodology/Principal Findings</h3><p>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 ¹⁵N-¹H 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.</p> <h3>Conclusions/Significance</h3><p>The current study provides important insights into the conservation of interactions and structures among different CTs of integrins.</p> </div

Assembly of 1-D and decanuclear cage compounds from copper halide, cyclohexenephosphonic acid, and 3-(2-pyridyl)pyrazole

<div><p>The reactions of cyclohexenephosphonic acid (C₆H₉PO₃H₂) and 3-(2-pyridyl)pyrazole (2-pyPzH) with copper(II) chloride and copper(II) bromide affords a 1-D compound [Cu(2-pyPz)Cl] (<b>1</b>) and a decanuclear [Cu₁₀(OH)₄(C₆H₉PO₃)₆(2-pyPz)₄] (<b>2</b>) cage complex. In <b>1</b>, adjacent copper ions are bridged by two 2-pyPz ligands into dimers, which are further linked by Cl⁻ into a ladder-like chain. Compound <b>2</b> has a decanuclear cage structure, the overall cage can be viewed as composed of two Cu₄(OH)₂(2-pyPz)₂ wings that are bridged by a central Cu₂P₂O₆ rim. Variable-temperature magnetic susceptibility studies indicate that both compounds show antiferromagnetic interactions between copper centers.</p></div

Supplemental Material, Supplemental_Table_1_(1) - The Exosomal Long Noncoding RNA aHIF is Upregulated in Serum From Patients With Endometriosis and Promotes Angiogenesis in Endometriosis

Supplemental Material, Supplemental_Table_1_(1) for The Exosomal Long Noncoding RNA aHIF is Upregulated in Serum From Patients With Endometriosis and Promotes Angiogenesis in Endometriosis by Jun-Jun Qiu, Xiao-Jing Lin, Ting-Ting Zheng, Xiao-Yan Tang, Ying Zhang, and Ke-Qin Hua in Reproductive Sciences</p

Folded conformation of myristoylated αX CT.

<p>A section of the two-dimensional ¹H-¹H NOESY spectrum of αX CT in DPC micelles showing NOE contacts among low-field resonances (6.5 ppm–9.0 ppm) with up-field resonances (0.8 ppm–4.5 ppm). A large number of NOE cross-peak indicates αX CT is well folded in DPC micelles. NOESY spectra were acquired in 200 mM DPC dissolved in 10 mM sodium phosphate buffer, pH 5.6, 308 K.</p

Summary of structural statistics of the twenty lowest energy structures of myristoylated αX CT in DPC micelles.

a<p>The RMSD values for the N-terminal helical region (residue 2–17) are in parentheses.</p

Docked structure of the αX/β2 CTs.

<p>Plausible interfacial residues of the complex of CTs of αX/β2 integrin. The polar face of the amphipathic helical structure of αX CT (in blue ribbon) appears to be engaged in multiple ionic and/or hydrogen bond interactions with the membrane proximal helix of β2 (in black ribbon). The probable mutual sidechain-sidechain packing among the non-polar and aromatic residues of αX CT with the β2 CT at their N-termini is represented by space filling.</p

Packing interactions in the αX CT in DPC micelles.

<p>Selected regions of two-dimensional ¹H-¹H NOESY spectra of the αX CT showing NOE contacts among; (panel A) aromatic ring proton resonances with the aliphatic sidechain resonances, (panel B) aromatic ring proton resonances of F5 and Y9, (panels C and D) sidechains of M12/I20 and A16/N24.</p

Secondary structure of the αX CT from chemical shift deviations.

<p>Bar diagrams representing deviation of ¹³Cα (top panel and CαH (bottom panel) chemical shifts from random coil values for amino acid residues of αX CT in DPC micelles.</p

Supplemental Material, Doc1 - The Exosomal Long Noncoding RNA aHIF is Upregulated in Serum From Patients With Endometriosis and Promotes Angiogenesis in Endometriosis

Supplemental Material, Doc1 for The Exosomal Long Noncoding RNA aHIF is Upregulated in Serum From Patients With Endometriosis and Promotes Angiogenesis in Endometriosis by Jun-Jun Qiu, Xiao-Jing Lin, Ting-Ting Zheng, Xiao-Yan Tang, Ying Zhang, and Ke-Qin Hua in Reproductive Sciences</p

Structures and interactions of the α CTs of integrins.

<p>(top panel) Ribbon representation of the 3-D structures of different a CTs determined in previous studies (panel A) αIIb CT of αIIb/β3 integirn, (panel B) αL CT of αLβ2 integrin, (panel C) αM CT of αMβ2 integrin. (bottom panel) Comparison of the complexes of α and β CTs of (panel A) αIIb/β3 integirn, (panel B) αLβ2 integrin and (panel C) αMβ2 integrin.</p