PSU Profiles
Last Name

Ira Ropson

TitleAssociate Professor
InstitutionCollege of Medicine
DepartmentBiochemistry and Molecular Biology
Address500 University Drive Hershey PA 17033
Mailbox: H171
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    Associate Professor of Biochemistry and Molecular Biology


    Biochemistry and Molecular Biology, Integrative Biosciences, Cell and Molecular Biology, MD/PhD Degree Program


    Ph.D., Johns Hopkins University, 1987
    Postdoctoral Training, University of Colorado, 1987-1988
    Postdoctoral Training, Washington University, 1988-1992


    Current efforts in this laboratory are focused on the folding, stability and function of a large family of all ß-sheet proteins, the intracellular lipid binding proteins. These proteins have very similar structures but diverse amino-acid sequences and ligand specificities and are crucial to hydrophobic ligand transport and utilization within the cell. We have shown that there are at least two intermediates present on the folding pathway for one of these proteins, intestinal fatty-acid binding protein (IFABP). These intermediates involve only one of the two tryptophans in the sequence of IFABP, and may act as folding initiation sites. Studies on other members of the family have shown surprising heterogeneity in the mechanism of folding for these structurally similar proteins. The overall rates of folding and unfolding vary by as much as 4 orders of magnitude for different members of the family. Further, the spectroscopic properties of the intermediates are generally not similar among these proteins, implying that the intermediate structures responsible for these spectroscopic properties are also different. We are using nuclear magnetic resonance, small angle x-ray scattering, fluorescence and circular dichroism to better describe the size, shape, and spectroscopic properties of these intermediates, both kinetically and at equilibrium. Little is known about the folding path or the mechanism of stabilization of any ß-sheet protein, emphasizing the importance of these studies to a general understanding of the protein folding problem.

    A related project is to determine the physical forces that stabilize this structural motif. This project uses site-directed mutagenesis and molecular dynamics calculations to determine the importance of hydrophobic packing, hydrogen bonding patterns, and buried charge neutralization to the overall stability of these ß-sheet proteins. The overall structure of these proteins is unusual, since there is a large internal solvent filled cavity in the apo-structures of all of these proteins, which is only partially filled by ligand after binding. The overall structure of the protein backbone changes very little when ligand binds, providing no obvious means of entry of the ligand to this buried pocket.

    Several proteins in this family are phosphorylated on a tyrosine by the insulin receptor, which suggests an additional regulatory function for these proteins. Phosphorylation may cause changes in overall protein stability, ligand affinity, and/or ligand flux within the cell. These proteins could serve as models for tyrosine phosphorylation and its effects on protein structure, which has important implications for gene regulation since so many regulatory proteins are tyrosine phosphorylated. There is evidence that one of these proteins may act as inhibitory growth factors for breast cancer cells in vitro, again suggesting an additional role for these proteins in the regulation of cell proliferation.

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. England MR, Purdy JG, Ropson IJ, Dalessio PM, Craven RC. Potential role for CA-SP in nucleating retroviral capsid maturation. J Virol. 2014 Jul; 88(13):7170-7. PMID: 24719425; PMCID: PMC4054415.
    2. Dalessio PM, Craven RC, Lokhandwala PM, Ropson IJ. Lethal mutations in the major homology region and their suppressors act by modulating the dimerization of the rous sarcoma virus capsid protein C-terminal domain. Proteins. 2013 Feb; 81(2):316-25. PMID: 23011855; PMCID: PMC3657841.
    3. Olson KC, Sun D, Chen G, Sharma AK, Amin S, Ropson IJ, Spratt TE, Lazarus P. Characterization of dibenzo[a,l]pyrene-trans-11,12-diol (dibenzo[def,p]chrysene) glucuronidation by UDP-glucuronosyltransferases. Chem Res Toxicol. 2011 Sep 19; 24(9):1549-59. PMID: 21780761; PMCID: PMC3177992.
    4. Basehore HK, Ropson IJ. Residual interactions in unfolded bile acid-binding protein by 19F NMR. Protein Sci. 2011 Feb; 20(2):327-35. PMID: 21280124; PMCID: PMC3048417.
    5. Ropson IJ, Boyer JA, Schaeffer BA, Dalessio PM. Comparison of the folding mechanism of highly homologous proteins in the lipid-binding protein family. Proteins. 2009 Jun; 75(4):799-806. PMID: 19003989.
      View in: PubMed
    6. Purdy JG, Flanagan JM, Ropson IJ, Craven RC. Retroviral capsid assembly: a role for the CA dimer in initiation. J Mol Biol. 2009 Jun 05; 389(2):438-51. PMID: 19361521; PMCID: PMC2996723.
    7. Purdy JG, Flanagan JM, Ropson IJ, Rennoll-Bankert KE, Craven RC. Critical role of conserved hydrophobic residues within the major homology region in mature retroviral capsid assembly. J Virol. 2008 Jun; 82(12):5951-61. PMID: 18400856; PMCID: PMC2395126.
    8. Ropson IJ, Boyer JA, Dalessio PM. A residual structure in unfolded intestinal fatty acid binding protein consists of amino acids that are neighbors in the native state. Biochemistry. 2006 Feb 28; 45(8):2608-17. PMID: 16489754.
      View in: PubMed
    9. Diep CQ, Peng G, Bewley M, Pilauri V, Ropson I, Hopper JE. Intragenic suppression of Gal3C interaction with Gal80 in the Saccharomyces cerevisiae GAL gene switch. Genetics. 2006 Jan; 172(1):77-87. PMID: 16219783; PMCID: PMC1456197.
    10. Dalessio PM, Fromholt SE, Ropson IJ. The role of Trp-82 in the folding of intestinal fatty acid binding protein. Proteins. 2005 Oct 01; 61(1):176-83. PMID: 16080148.
      View in: PubMed
    11. Dalessio PM, Boyer JA, McGettigan JL, Ropson IJ. Swapping core residues in homologous proteins swaps folding mechanism. Biochemistry. 2005 Mar 01; 44(8):3082-90. PMID: 15723553.
      View in: PubMed
    12. Burns-Hamuro LL, Dalessio PM, Ropson IJ. Replacement of proline with valine does not remove an apparent proline isomerization-dependent folding event in CRABP I. Protein Sci. 2004 Jun; 13(6):1670-6. PMID: 15152096; PMCID: PMC2279983.
    13. Rasimas JJ, Dalessio PA, Ropson IJ, Pegg AE, Fried MG. Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase. Protein Sci. 2004 Jan; 13(1):301-5. PMID: 14691244; PMCID: PMC2286524.
    14. Pastukhov AV, Ropson IJ. Fluorescent dyes as probes to study lipid-binding proteins. Proteins. 2003 Nov 15; 53(3):607-15. PMID: 14579352.
      View in: PubMed
    15. Rasimas JJ, Kanugula S, Dalessio PM, Ropson IJ, Fried MG, Pegg AE. Effects of zinc occupancy on human O6-alkylguanine-DNA alkyltransferase. Biochemistry. 2003 Feb 04; 42(4):980-90. PMID: 12549918.
      View in: PubMed
    16. Burns LL, Ropson IJ. Folding of intracellular retinol and retinoic acid binding proteins. Proteins. 2001 May 15; 43(3):292-302. PMID: 11288179.
      View in: PubMed
    17. Yeh SR, Ropson IJ, Rousseau DL. Hierarchical folding of intestinal fatty acid binding protein. Biochemistry. 2001 Apr 10; 40(14):4205-10. PMID: 11284675.
      View in: PubMed
    18. Ropson IJ, Yowler BC, Dalessio PM, Banaszak L, Thompson J. Properties and crystal structure of a beta-barrel folding mutant. Biophys J. 2000 Mar; 78(3):1551-60. PMID: 10692339; PMCID: PMC1300752.
    19. Dalessio PM, Ropson IJ. Beta-sheet proteins with nearly identical structures have different folding intermediates. Biochemistry. 2000 Feb 08; 39(5):860-71. PMID: 10653629.
      View in: PubMed
    20. Dalessio PM, Ropson IJ. pH dependence of the folding of intestinal fatty acid binding protein. Arch Biochem Biophys. 1998 Nov 15; 359(2):199-208. PMID: 9808761.
      View in: PubMed
    21. Burns LL, Dalessio PM, Ropson IJ. Folding mechanism of three structurally similar beta-sheet proteins. Proteins. 1998 Oct 01; 33(1):107-18. PMID: 9741849.
      View in: PubMed
    22. Ropson IJ, Dalessio PM. Fluorescence spectral changes during the folding of intestinal fatty acid binding protein. Biochemistry. 1997 Jul 15; 36(28):8594-601. PMID: 9214305.
      View in: PubMed
    23. Frieden C, Hoeltzli SD, Ropson IJ. NMR and protein folding: equilibrium and stopped-flow studies. Protein Sci. 1993 Dec; 2(12):2007-14. PMID: 8298453; PMCID: PMC2142323.
    24. Ropson IJ, Frieden C. Dynamic NMR spectral analysis and protein folding: identification of a highly populated folding intermediate of rat intestinal fatty acid-binding protein by 19F NMR. Proc Natl Acad Sci U S A. 1992 Aug 01; 89(15):7222-6. PMID: 1496015; PMCID: PMC49678.
    25. Ropson IJ, Gordon JI, Frieden C. Folding of a predominantly beta-structure protein: rat intestinal fatty acid binding protein. Biochemistry. 1990 Oct 16; 29(41):9591-9. PMID: 2271603.
      View in: PubMed
    26. Rudnick DA, McWherter CA, Adams SP, Ropson IJ, Duronio RJ, Gordon JI. Structural and functional studies of Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase produced in Escherichia coli. Evidence for an acyl-enzyme intermediate. J Biol Chem. 1990 Aug 05; 265(22):13370-8. PMID: 2198291.
      View in: PubMed
      View in: PubMed
    28. Rees BB, Ropson IJ, Hand SC. Kinetic properties of hexokinase under near-physiological conditions. Relation to metabolic arrest in Artemia embryos during anoxia. J Biol Chem. 1989 Sep 15; 264(26):15410-7. PMID: 2768270.
      View in: PubMed
    29. Ropson IJ, Powers DA. The allelic isozymes of hexose-6-phosphate dehydrogenase isolated from Fundulus heteroclitus: physical characteristics and kinetic properties. Mol Biol Evol. 1989 Mar; 6(2):171-85. PMID: 2716518.
      View in: PubMed
    30. Ropson IJ, Powers DA. A novel dehydrogenase reaction mechanism for hexose-6-phosphate dehydrogenase isolated from the teleost Fundulus heteroclitus. J Biol Chem. 1988 Aug 25; 263(24):11697-703. PMID: 3403551.
      View in: PubMed
    31. Fishbein JC, Place AR, Ropson IJ, Powers DA, Sofer W. Thin-layer peptide mapping: quantitative analysis and sequencing at the nanomole level. Anal Biochem. 1980 Oct; 108(1):193-201. PMID: 6779667.
      View in: PubMed
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