Identification of Novel Peptide Substrates for Protein Farnesyltransferase Reveals Two Substrate Classes with Distinct Sequence Selectivities

Journal of Molecular Biology

Volumn 395, Issue 1, 2010, Pages 176-190

  Hougland, James L ^a   Hicks, Katherine A ^b   Hartman, Heather L ^a   Kelly, Rebekah A ^a   Watt, Terry J ^a   Fierke, Carol A ^a,b  

^a UNIVERSITY OF MICHIGAN   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

farnesylation; peptide library; prenylation; protein farnesyltransferase; substrate specificity

Indexed keywords

DIMETHYLALLYLTRANSFERASE; GLYCINE; LAMIN A; LAMIN C; METHIONINE; PHENYLALANINE; TETRASPANIN;

AMINO ACID SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME SPECIFICITY; ENZYME SUBSTRATE; HUMAN; PRENYLATION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN TARGETING;

EID: 70450224430     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2009.10.038     Document Type: Article

References (69)

1. Zhang F.L., and Casey P.J. Protein prenylation: molecular mechanisms and functional consequences. Annu. Rev. Biochem. 65 (1996) 241-269
2. Benetka W., Koranda M., and Eisenhaber F. Protein prenylation: an (almost) comprehensive overview on discovery history, enzymology, and significance in physiology and disease. Monatsh. Chem. 137 (2006) 1241-1281
3. Casey P.J., and Seabra M.C. Protein prenyltransferases. J. Biol. Chem. 271 (1996) 5289-5292
4. Casey P.J. Lipid modifications of g proteins. Curr. Opin. Cell Biol. 6 (1994) 219-225
5. Marshall C.J. Protein prenylation: a mediator of protein-protein interactions. Science 259 (1993) 219-225
6. Sebti S.M., and Hamilton A.D. Farnesyltransferase inhibitors in cancer therapy. In: Teicher B.A. (Ed). Cancer Drug Discovery and Development vol. 8 (2001), Humana Press, Totowa, NJ
7. Kho Y., Kim S.C., Jiang C., Barma D., Kwon S.W., Cheng J.K., et al. A tagging-via-substrate technology for detection and proteomics of farnesylated proteins. Proc. Natl Acad. Sci. USA 101 (2004) 12479-12484
8. Maurer-Stroh S., Koranda M., Benetka W., Schneider G., Sirota F.L., and Eisenhaber F. Towards complete sets of farnesylated and geranylgeranylated proteins. PLoS Comput. Biol. 3 (2007) 634-648
9. Maurer-Stroh S., and Eisenhaber F. Refinement and prediction of protein prenylation motifs. Genome Biol. 6 (2005) R55
10. Reid T.S., Terry K.L., Casey P.J., and Beese L.S. Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity. J. Mol. Biol. 343 (2004) 417-433
11. Caplin B.E., Hettich L.A., and Marshall M.S. Substrate characterization of the Saccharomyces cerevisiae protein farnesyltransferase and type-I protein geranylgeranyltransferase. Biochim. Biophys. Acta 1205 (1994) 39-48
12. Omer C.A., Karl A.M., Diehl R.E., Prendergast G.C., Powers S., Allen C.M., and Kohl N.E. Characterization of recombinant human farnesyl-protein transferase: cloning, expression, farnesyl diphosphate binding, and functional homology with yeast prenyl-protein transferases. Biochemistry 32 (1993) 5167-5176
13. Reiss Y., Stradley S.J., Gierasch L.M., Brown M.S., and Goldstein J.L. Sequence requirement for peptide recognition by rat brain p2l ras protein farnesyltransferase. Proc. Natl Acad. Sci. USA 88 (1991) 732-736
14. Moores S.L., Schaber M.D., Mosser S.D., Rands E., O'Hara M.B., Garsky V.M., et al. Sequence dependence of protein isoprenylation. J. Biol. Chem. 266 (1991) 14603-14610
15. Yokoyama K., Goodwin G.W., Ghomashchi F., and Gelb M.H. A protein geranylgeranyltransferase from bovine brain: implications for protein prenylation specificity. Proc. Natl Acad. Sci. USA 88 (1991) 5302-5306
16. Casey P.J., Thissen J.A., and Moomaw J.F. Enzymatic modification of proteins with a geranylgeranyl isoprenoid. Proc. Natl Acad. Sci. USA 88 (1991) 8631-8635
17. Fu H.W., and Casey P.J. Enzymology and biology of CaaX protein prenylation. Recent Prog. Horm. Res. 54 (1999) 315-342
18. Hicks K.A., Hartman H.L., and Fierke C.A. Upstream polybasic region in peptides enhances dual specificity for prenylation by both farnesyltransferase and geranylgeranyltransferase type I. Biochemistry 44 (2005) 15325-15333
19. Hougland J.L., Lamphear C.L., Scott S.A., Gibbs R.A., and Fierke C.A. Context-dependent substrate recognition by protein farnesyltransferase. Biochemistry 48 (2009) 1691-1701
20. Hartman H.L., Hicks K.A., and Fierke C.A. Peptide specificity of protein prenyltransferases is determined mainly by reactivity rather than binding affinity. Biochemistry 44 (2005) 15314-15324
21. Chen Z., Sun J.Z., Pradines A., Favre G., Adnane J., and Sebti S.M. Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice. J. Biol. Chem. 275 (2000) 17974-17978
22. Maurer-Stroh S., Washietl S., and Eisenhaber F. Protein prenyltransferases: anchor size, pseudogenes and parasites. Biol. Chem. 384 (2003) 977-989
23. Gelb M.H., Van Voorhis W.C., Buckner F.S., Yokoyama K., Eastman R., Carpenter E.P., et al. Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics. Mol. Biochem. Parasitol. 126 (2003) 155-163
24. Khosravi-Far R., Cox A.D., Kato K., and Der C.J. Protein prenylation: key to ras function and cancer intervention?. Cell Growth Differ. 3 (1992) 461-469
25. Gibbs J.B., and Oliff A. The potential of farnesyltransferase inhibitors as cancer chemotherapeutics. Annu. Rev. Pharmacol. 37 (1997) 143-166
26. Sebti S.M., and Hamilton A.D. Farnesyltransferase and geranylgeranyltransferase I inhibitors and cancer therapy: lessons from mechanism and bench-to-bedside translational studies. Oncogene 19 (2000) 6584-6593
27. Roskoski R. Protein prenylation: a pivotal posttranslational process. Biochem. Biophys. Res. Commun. 303 (2003) 1-7
28. Sepp-Lorenzino L., Ma Z., Rands E., Kohl N.E., Gibbs J.B., Oliff A., and Rosen N. A peptidomimetic inhibitor of farnesylprotein transferase blocks the anchorage dependent and independent growth of human tumor cell lines. Cancer Res. 55 (1995) 5302-5309
29. Pompliano D.L., Gomez R.P., and Anthony N.J. Intramolecular fluorescence enhancement: a continuous assay of ras farnesyl:protein transferase. J. Am. Chem. Soc. 114 (1992) 7945-7946
30. Gasteiger E., Gattiker A., Hoogland C., Ivanyi I., Appel R.D., and Bairoch A. Expasy: the proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res. 31 (2003) 3784-3788
31. Cox A.D., and Der C.J. Farnesyltransferase inhibitors and cancer treatment: targeting simply Ras?. Biochim. Biophys. Acta 1333 (1997) F51-F71
32. Boutin J.A., Marande W., Petit L., Loynel A., Desmet C., Canet E., and Fauchere J.L. Investigation of S-farnesyl transferase substrate specificity with combinatorial tetrapeptide libraries. Cell. Signalling 11 (1999) 59-69
33. Fersht A. Structure and Mechanism in Protein Science (1999), W. H. Freeman and Company, New York, NY
34. Spence R.A., Hightower K.E., Terry K.L., Beese L.S., Fierke C.A., and Casey P.J. Conversion of Tyr361 beta to Leu in mammalian protein farnesyltransferase impairs product release but not substrate recognition. Biochemistry 39 (2000) 13651-13659
35. Furfine E.S., Leban J.J., Landavazo A., Moomaw J.F., and Casey P.J. Protein farnesyltransferase: kinetics of farnesyl pyrophosphate binding and product release. Biochemistry 34 (1995) 6857-6862
36. Pickett J.S., Bowers K.E., Hartman H.L., Fu H.W., Embry A.C., Casey P.J., and Fierke C.A. Kinetic studies of protein farnesyltransferase mutants establish active substrate conformation. Biochemistry 42 (2003) 9741-9748
37. Zimmerman K.K., Scholten J.D., Huang C.C., Fierke C.A., and Hupe D.J. High-level expression of rat farnesyl:protein transferase in Escherichia coli as a translationally coupled heterodimer. Protein Expr. Purif. 14 (1998) 395-402
38. Long S.B., Hancock P.J., Kral A.M., Hellinga H.W., and Beese L.S. The crystal structure of human protein farnesyltransferase reveals the basis for inhibition by CaaX tetrapeptides and their mimetics. Proc. Natl Acad. Sci. USA 98 (2001) 12948-12953
39. Pompliano D.L., Rands E., Schaber M.D., Mosser S.D., Anthony N.J., and Gibbs J.B. Steady-state kinetic mechanism of ras farnesyl-protein transferase. Biochemistry 31 (1992) 3800-3807
40. Pais J.E., Bowers K.E., Stoddard A.K., and Fierke C.A. A continuous fluorescent assay for protein prenyltransferases measuring diphosphate release. Anal. Biochem. 345 (2005) 302-311
41. Pompliano D.L., Schaber M.D., Mosser S.D., Omer C.A., and Gibbs J.B. Isoprenoid diphosphate utilization by recombinant human farnesyl:protein transferase: interactive binding between substrates and a preferred kinetic pathway. Biochemistry 32 (1993) 8341-8347
42. Tschantz W.R., Furfine E.S., and Casey P.J. Substrate binding is required for release of product from mammalian protein farnesyltransferase. J. Biol. Chem. 272 (1997) 9989-9993
43. Long S.B., Casey P.J., and Beese L.S. Reaction path of protein farnesyltransferase at atomic resolution. Nature 419 (2002) 645-650
44. Pickett J.S., Bowers K.E., Hartman H.L., Fu H.-W., Embry A.C., Casey P.J., and Fierke C.A. Kinetic studies of protein farnesyltransferase mutants establish active substrate conformation. Biochemistry 42 (2003) 9741-9748
45. Pais J.E., Bowers K.E., and Fierke C.A. Measurement of the alpha-secondary kinetic isotope effect for the reaction catalyzed by mammalian protein farnesyltransferase. J. Am. Chem. Soc. 128 (2006) 15086-15087
46. Reiss Y., Seabra M.C., Armstrong S.A., Slaughter C.A., and Brown M.S. Nonidentical subunits of p21h-ras farnesyltransferase. Peptide binding and farnesyl pyrophosphate carrier functions. J. Biol. Chem. 266 (1991) 10672-10677
47. Roskoski Jr. R., and Ritchie P. Role of the carboxyterminal residue in peptide binding to protein farnesyltransferase and protein geranylgeranyltransferase. Arch. Biochem. Biophys. 356 (1998) 167-176
48. Huang C.C., Hightower K.E., and Fierke C.A. Mechanistic studies of rat protein farnesyltransferase indicate an associative transition state. Biochemistry 39 (2000) 2593-2602
49. Lowry D.R., and Willumsen B.M. New clue to ras lipid glue. Nature 341 (1989) 384-385
50. Casey P.J., Solski P.A., Der C.J., and Buss J.E. P21ras is modified by a farnesyl isoprenoid. Proc. Natl Acad. Sci. USA 86 (1989) 8323-8327
51. Reiss Y., Goldstein J.L., Seabra M.C., and Brown M.S. Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides. Cell 62 (1990) 81-88
52. Goldstein J.L., Brown M.S., Stradley S.J., Reiss Y., and Gierasch L.M. Nonfarnesylated tetrapeptide inhibitors of protein farnesyltransferase. J. Biol. Chem. 266 (1991) 15575-15578
53. Carboni J.M., Yan N., Cox A.D., Bustelo X., Graham S.M., Lynch M.J., et al. Farnesyltransferase inhibitors are inhibitors of ras but not r-ras2/tc21 transformation. Oncogene 10 (1995) 1905-1913
54. Rowell C.A., Kowalczyk J.J., Lewis M.D., and Garcia A.M. Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo. J. Biol. Chem. 272 (1997) 14093-14097
55. Whyte D.B., Kirschmeier P., Hockenberry T.N., Nunez-Oliva I., James L., Catino J.J., et al. K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J. Biol. Chem. 272 (1997) 14459-14464
56. Adamson P., Marshall C.J., Hall A., and Tilbrook P.A. Post-translational modification of p21rho proteins. J. Biol. Chem. 267 (1992) 20033-20038
57. Yokoyama K., Zimmerman K., Scholten J., and Gelb M.H. Differential prenyl pyrophosphate binding to mammalian protein geranylgeranyltransferase-I and protein farnesyltransferase and its consequence on the specificity of protein prenylation. J. Biol. Chem. 272 (1997) 3944-3952
58. Baron R., Fourcade E., Lajoie-Mazenc I., Allal C., Couderc B., Barbaras R., et al. RhoB prenylation is driven by the three carboxyl-terminal amino acids of the protein: evidenced in vivo by an anti-farnesyl cysteine antibody. Proc. Natl Acad. Sci. USA 97 (2000) 11626-11631
59. Troutman J.M., Andres D.A., and Spielmann H.P. Protein farnesyl transferase target selectivity is dependent upon peptide stimulated product release. Biochemistry 46 (2007) 11299-11309
60. Haataja L., Groffen J., and Heisterkamp N. Characterization of rac3 a novel member of the rho family. J. Biol. Chem. 272 (1997) 20384-20388
61. Tsubakimoto K., Matsumoto K., Abe H., Ishii J., Mutsuki A., Kaibuchi K., and Endo T. Small GTPase RhoD suppresses cell migration and cytokinesis. Oncogene 18 (1999) 2431-2440
62. Krzysiak A.J., Scott S.A., Hicks K.A., Fierke C.A., and Gibbs R.A. Evaluation of protein farnesyltransferase substrate specificity using synthetic peptide libraries. Bioorg. Med. Chem. Lett. 17 (2007) 5548-5551
63. Krzysiak A.J., Rawat D.S., Scott S.A., Pais J.E., Handley M., Harrison M.L., et al. Combinatorial modulation of protein prenylation. ACS Chem. Biol. 2 (2007) 385-389
64. Riddles P.W., Blakeley R.L., and Zerner B. Ellman's reagent: 5,5′-dithiobis(2-nitrobenzoic acid)-a reexamination. Anal. Biochem. 94 (1979) 75-81
65. Cassidy P.B., Dolence J.M., and Poulter C.D. Continuous fluorescence assay for protein farnesyltransferase. Methods Enzymol. 250 (1995) 30-43
66. Bowers K.E., and Fierke C.A. Positively charged side chains in protein farnesyltransferase enhance catalysis by stabilizing the formation of the diphosphate leaving group. Biochemistry 43 (2004) 5256-5265
67. Chehade K.A.H., Kiegiel K., Isaacs R.J., Pickett J.S., Bowers K.E., Fierke C.A., et al. Photoaffinity analogues of farnesyl pyrophosphate transferable by protein farnesyl transferase. J. Am. Chem. Soc. 124 (2002) 8206-8219
68. Hightower K.E., Huang C.C., Casey P.J., and Fierke C.A. H-Ras peptide and protein substrates bind protein farnesyltransferase as an ionized thiolate. Biochemistry 37 (1998) 15555-15562
69. Lakowicz J.R. Principles of Fluorescence Spectroscopy. 2nd edit. (1999), Kluwer Academic/Plenum Publishers, New York, NY