Light-activated rhodopsin induces structural binding motif in G protein α subunit

A large superfamily of transmembrane receptors control cellular responses to diverse extracellular signals by catalyzing activation of specific types of heterotrimeric GTP-binding proteins. How these receptors recognize and promote nucleotide exchange on G protein α subunits to initiate signal amplification is unknown. The three-dimensional structure of the transducin (Gt) α subunit C-terminal undecapeptide Gtα(340–350) IKENLKDCGLF was determined by transferred nuclear Overhauser effect spectroscopy while it was bound to photoexcited rhodopsin. Light activation of rhodopsin causes a dramatic shift from a disordered conformation of Gtα(340–350) to a binding motif with a helical turn followed by an open reverse turn centered at Gly-348, a helix-terminating C capping motif of an αL type. Docking of the NMR structure to the GDP-bound x-ray structure of Gt reveals that photoexcited rhodopsin promotes the formation of a continuous helix over residues 325–346 terminated by the C-terminal helical cap with a unique cluster of crucial hydrophobic side chains. A molecular mechanism by which activated receptors can control G proteins through reversible conformational changes at the receptor–G protein interface is demonstrated.

A DNA damage and stress inducible G protein-coupled receptor blocks cells in G2/M

Cell cycle progression is monitored by highly coordinated checkpoint machinery, which is activated to induce cell cycle arrest until defects like DNA damage are corrected. We have isolated an anti-proliferative cell cycle regulator named G2A (for G2 accumulation), which is predominantly expressed in immature T and B lymphocyte progenitors and is a member of the seven membrane-spanning G protein-coupled receptor family. G2A overexpression attenuates the transformation potential of BCR-ABL and other oncogenes, and leads to accumulation of cells at G2/M independently of p53 and c-Abl. G2A can be induced in lymphocytes and to a lesser extent in nonlymphocyte cell lines or tissues by multiple stimuli including different classes of DNA-damaging agents and serves as a response to damage and cellular stimulation which functions to slow cell cycle progression.

Crystal structure of the ectodomain of Methuselah, a Drosophila G protein-coupled receptor associated with extended lifespan

The Drosophila mutant methuselah (mth) was identified from a screen for single gene mutations that extended average lifespan. Mth mutants have a 35% increase in average lifespan and increased resistance to several forms of stress, including heat, starvation, and oxidative damage. The protein affected by this mutation is related to G protein-coupled receptors of the secretin receptor family. Mth, like secretin receptor family members, has a large N-terminal ectodomain, which may constitute the ligand binding site. Here we report the 2.3-Å resolution crystal structure of the Mth extracellular region, revealing a folding topology in which three primarily β-structure-containing domains meet to form a shallow interdomain groove containing a solvent-exposed tryptophan that may represent a ligand binding site. The Mth structure is analyzed in relation to predicted Mth homologs and potential ligand binding features.

Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors

The telomerase enzyme is a potential therapeutic target in many human cancers. A series of potent inhibitors has been designed by computer modeling, which exploit the unique structural features of quadruplex DNA. These 3,6,9-trisubstituted acridine inhibitors are predicted to interact selectively with the human DNA quadruplex structure, as a means of specifically inhibiting the action of human telomerase in extending the length of single-stranded telomeric DNA. The anilino substituent at the 9-position of the acridine chromophore is predicted to lie in a third groove of the quadruplex. Calculated relative binding energies predict enhanced selectivity compared with earlier 3,6-disubstituted compounds, as a result of this substituent. The ranking order of energies is in accord with equilibrium binding constants for quadruplex measured by surface plasmon resonance techniques, which also show reduced duplex binding compared with the disubstituted compounds. The 3,6,9-trisubstututed acridines have potent in vitro inhibitory activity against human telomerase, with EC50 values of up to 60 nM.

Life in New Bedford a hundred years ago; a chronicle of the social, religious and commercial history of the period as recorded in a diary kept by Joseph R. Anthony;

Mode of access: Internet.

The annual address delivered before the Diagnothian and Goethean Literary Societies of Marshall College, Mercersburg, Pa., on the connection between government, and science and literature ... September 8, 1846.

Mode of access: Internet.

Nominations before the Senate Armed Services Committee, first session, 105th Congress : hearings before the Committee on Armed Services, United States Senate, One Hundred Fifth Congress, first session, on nominations of William S. Cohen; Federico F. Peǹa; Keith R. Hall; Gen. Wesley K. Clark, USA; Lt. Gen. Anthony C. Zinni, USMC; Rudy F. de Leon; John J. Hamre; Gen. Henry H. Shelton, USA; Gen. Michael E. Ryan, USAF; Adm. Harold W. Gehman, Jr., USN; Lt. Gen. Charles E. Wilhelm, USMC; Dr. Jacques S. Gansler; Lt. Gen. Peter J. Schoomaker, USA; Lt. Gen. John A. Gordon, USAF; Robert M. Walker; Jerry MacArthur Hultin; F. Whitten Peters; William J. Lynn III, January 22; February 5; March 6; July 9, 17, 24; September 9, 16; October 1, 23, 30; November 8, 1997.

Shipping list no.: 98-0179-P.

Antonii de Rooy ... Conjecturae criticae in diversorum poëtarum spectacula : M. Valerii Martialis epigrammatum libros XIV et P. Cornelli Severi Aetnam : accedit R.M.V.G epistola crítica ... M. Val. Martialis.

Mode of access: Internet.

Spenser. Book II of the Faery queene. : ed. by G.W. Kitchin.

"A new glossary has been written for the present edition by the Rev. A. L. Mayhew" (p.[248]-300) --Intro.

Old Blackfriars; a story of the days of Sir Anthony Van Dyck,

Title vignette (portrait)

Marshall, Wetzel and Tyler Counties,

"Soil survey of Marshall, Wetzel and Tyler Counties, W. Va., by Thos. A. Caine, E.R. Allen, H. Jennings, and G.W. Tailby, jr." p. 599-635.

School of Nursing Class of 1991

Top Row: Lisa A. Anton, Karen M. Banish, Sherry L. Bendele, Lori Bishop, Rossana Biundo, Jennifer Brooks, Stefanie J. Brown, Kimberly J. Coleman, Christine M. Decker, Mary Jo Diebold, Molly Donohue, Mary C. Dubois, Meggan C. Ebert

Row 2: Michelle Fox, Ann Marie Gergely, Nina N. Giglio, Stephen Gniewek, Jennifer K. Gollon, Laura E. Gregorius, Shiree A. Hamilton, Corinne R. Hardecki, Yoline M. Hargrave, Raina C. Hartitz, Dana M. Hocking, Andrea E. Jarrett

Row 3: Nancy Johnson, Harjot Kaur, Doreen M. Kinney, Kristine Boyle, Michele Phillips, Anthony Stewart, Pamela Blumson, Lisa Rudin, Lisa Eby, Christina Koehlmann, Julie A. Kolar, Shelly M. Kraiza

Row 4: Cindy Kvarnberg, Beth Anne Lannan, Martha Lasley, James A. Lowery

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