Abstract

Mature T-cell Proliferation Factor 1 (MTCP-1) and TCL-1 genes form a novel family that is involved in T-cell malignancies and lymphoid proliferation. TCL-1 and MTCP-1 oncogenes encode for 14kDa proteins that share 41% identical amino acid residues but have no significant similarities with other known proteins. The crystal structure of MTCP-1 will be used to design mutations to study the function, and peptide analogs as potential drugs for treatment of T-cell malignancies. Crystals of MTCP-1 grow in space group P6 with the unit cell dimensions of a = b = 61.41 and c = 87.31?. The crystals diffract to 2.5-2.0? resolution, three potential heavy atom derivatives have been found, and phases result in a partially interpretable electron density map. There are two problems: the X-ray data are weak and radiation decay reduces the accuracy of the measurements; and the derivatives are not mutually isomorphous. Synchrotron time is requested to obtain accurate high resolution data for the native and anomalous data for the derivatives in order to improve the phases. We are also preparing selenomethionine enriched MTCP-1 for MAD phasing.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR001646-16
Application #
6281315
Study Section
Project Start
1998-09-15
Project End
1999-08-14
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
16
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Cornell University
Department
Type
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850

  Publications

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

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