The interferons are cytokines exhibiting antiviral, antitumor and immunomodulatory effects. At the molecular level these biological effects are the result of a chain of intracellular events, which is triggered outside the cell by the interaction of the ligand with specific transmembrane receptors. Interferon-g (IFN-g) is a 31kD homodimer. It binds two distinct receptors: the a-chain and the b-chain, to form a complex with the stoichiometry 1:2:2, one dimeric ligand and two copies of each receptor. The structure of a 1:2 complex (dimeric ligand and two a-chains) has been determined to about 3 _ resolution (MR Walter, WT Windsor, TL Naganbhushan, DJ Lundelll, kCA Lunn, PJ Zauodny, SK Narula, Nature 376:230, 1995; SE Ealick personal communication). We have constructed a single-chain IFN-g, which only binds a single a-chain ECD. These crystals diffract to 2 _ resolution. We collected 2 _ data a beam line A1 last month. A molecular replacement solution was obtained. There are two copies of the receptor complex in the asymmetric unit. Refinement has been initiated withthe 89,000 unique data. The current R value is 26% and the maps reveal significant detail in the protein structure and the solvation model.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001646-14
Application #
5223546
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1996
Total Cost
Indirect Cost
Kozlov, Guennadi; Wong, Kathy; Gehring, Kalle (2018) Crystal structure of the Legionella effector Lem22. Proteins 86:263-267
Ménade, Marie; Kozlov, Guennadi; Trempe, Jean-François et al. (2018) Structures of ubiquitin-like (Ubl) and Hsp90-like domains of sacsin provide insight into pathological mutations. J Biol Chem 293:12832-12842
Xu, Jie; Kozlov, Guennadi; McPherson, Peter S et al. (2018) A PH-like domain of the Rab12 guanine nucleotide exchange factor DENND3 binds actin and is required for autophagy. J Biol Chem 293:4566-4574
Dean, Dexter N; Rana, Pratip; Campbell, Ryan P et al. (2018) Propagation of an A? Dodecamer Strain Involves a Three-Step Mechanism and a Key Intermediate. Biophys J 114:539-549
Chen, Yu Seby; Kozlov, Guennadi; Fakih, Rayan et al. (2018) The cyclic nucleotide-binding homology domain of the integral membrane protein CNNM mediates dimerization and is required for Mg2+ efflux activity. J Biol Chem 293:19998-20007
Xu, Caishuang; Kozlov, Guennadi; Wong, Kathy et al. (2016) Crystal Structure of the Salmonella Typhimurium Effector GtgE. PLoS One 11:e0166643
Cogliati, Massimo; Zani, Alberto; Rickerts, Volker et al. (2016) Multilocus sequence typing analysis reveals that Cryptococcus neoformans var. neoformans is a recombinant population. Fungal Genet Biol 87:22-9
Oot, Rebecca A; Kane, Patricia M; Berry, Edward A et al. (2016) Crystal structure of yeast V1-ATPase in the autoinhibited state. EMBO J 35:1694-706
Lucido, Michael J; Orlando, Benjamin J; Vecchio, Alex J et al. (2016) Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry. Biochemistry 55:1226-38
Bauman, Joseph D; Harrison, Jerry Joe E K; Arnold, Eddy (2016) Rapid experimental SAD phasing and hot-spot identification with halogenated fragments. IUCrJ 3:51-60

Showing the most recent 10 out of 375 publications