Structural basis of recognition of farnesylated and methylated KRAS4b by PDEd

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 44, 2016, Pages E6766-E6775

  Dharmaiah, Srisathiyanarayanan ^a   Bindu, Lakshman ^a   Tran, Timothy H ^a   Gillette, William K ^a   Frank, Peter H ^a   Ghirlando, Rodolfo ^b   Nissley, Dwight V ^a   Esposito, Dominic ^a   McCormick, Frank ^a,c   Stephen, Andrew G ^a   Simanshu, Dhirendra K ^a  

^a FREDERICK NATIONAL LABORATORY FOR CANCER RESEARCH   (United States)

^b NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

KRAS PDEd complex; KRAS4b; Phosphodiesterase ; Prenylation; Protein protein interaction

Indexed keywords

ASPARAGINASE; KRAS4A PROTEIN; KRAS4B PROTEIN; PHOSPHODIESTERASE; PHOSPHODIESTERASE SIGMA; RAC1 PROTEIN; RALA PROTEIN; RALB PROTEIN; UNCLASSIFIED DRUG; CYCLIC GMP PHOSPHODIESTERASE; PROTEIN BINDING; PROTEIN P21; RAC1 PROTEIN, HUMAN; RAL PROTEIN; RALA PROTEIN, HUMAN; RALB PROTEIN, HUMAN;

CELL MEMBRANE; CONFERENCE PAPER; CONSERVED SEQUENCE; CONTROLLED STUDY; FARNESYLATION; ISOTHERMAL TITRATION CALORIMETRY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN METHYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; SEDIMENTATION RATE; SEQUENCE ANALYSIS; SIGNAL TRANSDUCTION; STRUCTURE ANALYSIS; AMINO ACID SEQUENCE; BINDING SITE; CHEMISTRY; CONFORMATION; GENETICS; HUMAN; METABOLISM; METHYLATION; MOLECULAR MODEL; MUTATION; ONCOGENE RAS; PHYSIOLOGY; PROTEIN DOMAIN; PROTEIN PRENYLATION; X RAY CRYSTALLOGRAPHY;

3',5'-CYCLIC-GMP PHOSPHODIESTERASES; AMINO ACID SEQUENCE; BINDING SITES; CELL MEMBRANE; CRYSTALLOGRAPHY, X-RAY; GENES, RAS; HUMANS; METHYLATION; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MUTATION; PROTEIN BINDING; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN PRENYLATION; PROTO-ONCOGENE PROTEINS P21(RAS); RAC1 GTP-BINDING PROTEIN; RAL GTP-BINDING PROTEINS; SEQUENCE ANALYSIS;

EID: 84994644427     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1615316113     Document Type: Article

References (61)

1. Prior IA, Lewis PD, Mattos C (2012) A comprehensive survey of Ras mutations in cancer. Cancer Res 72(10): 2457-2467.
2. Barbacid M (1987) ras genes. Annu Rev Biochem 56: 779-827.
3. Forbes SA, et al. (2015) COSMIC: Exploring the world's knowledge of somatic mutations in human cancer. Nucleic Acids Res 43(Database issue): D805-D811.
4. Bourne HR, Sanders DA, McCormick F (1991) The GTPase superfamily: Conserved structure and molecular mechanism. Nature 349(6305): 117-127.
5. Wittinghofer A, Pai EF (1991) The structure of Ras protein: A model for a universal molecular switch. Trends Biochem Sci 16(10): 382-387.
6. Takai Y, Sasaki T, Matozaki T (2001) Small GTP-binding proteins. Physiol Rev 81(1): 153-208.
7. Vigil D, Cherfils J, Rossman KL, Der CJ (2010) Ras superfamily GEFs and GAPs: Validated and tractable targets for cancer therapy? Nat Rev Cancer 10(12): 842-857.
8. Cherfils J, Zeghouf M (2013) Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiol Rev 93(1): 269-309.
9. Bos JL, Rehmann H, Wittinghofer A (2007) GEFs and GAPs: Critical elements in the control of small G proteins. Cell 129(5): 865-877.
10. Stephen AG, Esposito D, Bagni RK, McCormick F (2014) Dragging ras back in the ring. Cancer Cell 25(3): 272-281.
11. Cox AD, Der CJ (2010) Ras history: The saga continues. Small GTPases 1(1): 2-27.
12. Quinlan MP, Settleman J (2009) Isoform-specific ras functions in development and cancer. Future Oncol 5(1): 105-116.
13. Nussinov R, Tsai CJ, Chakrabarti M, Jang H (2016) A new view of Ras isoforms in cancers. Cancer Res 76(1): 18-23.
14. Reid TS, Terry KL, Casey PJ, Beese LS (2004) Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity. J Mol Biol 343(2): 417-433.
15. Hancock JF, Paterson H, Marshall CJ (1990) A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane. Cell 63(1): 133-139.
16. Manolaridis I, et al. (2013) Mechanism of farnesylated CAAX protein processing by the intramembrane protease Rce1. Nature 504(7479): 301-305.
17. Yang J, et al. (2011) Mechanism of isoprenylcysteine carboxyl methylation from the crystal structure of the integral membrane methyltransferase ICMT. Mol Cell 44(6): 997-1004.
18. Berndt N, Hamilton AD, Sebti SM (2011) Targeting protein prenylation for cancer therapy. Nat Rev Cancer 11(11): 775-791.
19. Whyte DB, et al. (1997) K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J Biol Chem 272(22): 14459-14464.
20. Chandra A, et al. (2011) The GDI-like solubilizing factor PDEd sustains the spatial organization and signalling of Ras family proteins. Nat Cell Biol 14(2): 148-158.
21. Baehr W (2014) Membrane protein transport in photoreceptors: The function of PDEd: The Proctor lecture. Invest Ophthalmol Vis Sci 55(12): 8653-8666.
22. Zhang H, et al. (2004) Photoreceptor cGMP phosphodiesterase delta subunit (PDEdelta) functions as a prenyl-binding protein. J Biol Chem 279(1): 407-413.
23. Weise K, et al. (2012) Dissociation of the K-Ras4B/PDEd complex upon contact with lipid membranes: Membrane delivery instead of extraction. J Am Chem Soc 134(28): 11503-11510.
24. Schmick M, et al. (2014) KRas localizes to the plasma membrane by spatial cycles of solubilization, trapping and vesicular transport. Cell 157(2): 459-471.
25. Schmick M, Kraemer A, Bastiaens PI (2015) Ras moves to stay in place. Trends Cell Biol 25(4): 190-197.
26. Ismail SA, et al. (2011) Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo. Nat Chem Biol 7(12): 942-949.
27. Nancy V, Callebaut I, El Marjou A, de Gunzburg J (2002) The delta subunit of retinal rod cGMP phosphodiesterase regulates the membrane association of Ras and Rap GTPases. J Biol Chem 277(17): 15076-15084.
28. Zimmermann G, et al. (2013) Small molecule inhibition of the KRAS-PDEd interaction impairs oncogenic KRAS signalling. Nature 497(7451): 638-642.
29. Chen YX, et al. (2010) Synthesis of the Rheb and K-Ras4B GTPases. Angew Chem Int Ed Engl 49(35): 6090-6095.
30. Fansa EK, O'Reilly NJ, Ismail S, Wittinghofer A (2015) The N- and C-terminal ends of RPGR can bind to PDE6d. EMBO Rep 16(12): 1583-1585.
31. Tsai FD, et al. (2015) K-Ras4A splice variant is widely expressed in cancer and uses a hybrid membrane-targeting motif. Proc Natl Acad Sci USA 112(3): 779-784.
32. Karan S, Zhang H, Li S, Frederick JM, Baehr W (2008) A model for transport of membrane-associated phototransduction polypeptides in rod and cone photoreceptor inner segments. Vision Res 48(3): 442-452.
33. Cook TA, Ghomashchi F, Gelb MH, Florio SK, Beavo JA (2000) Binding of the delta subunit to rod phosphodiesterase catalytic subunits requires methylated, prenylated C-termini of the catalytic subunits. Biochemistry 39(44): 13516-13523.
34. Hanzal-Bayer M, Linari M, Wittinghofer A (2005) Properties of the interaction of Arflike protein 2 with PDEdelta. J Mol Biol 350(5): 1074-1082.
35. Fansa EK, Kfsling SK, Zent E, Wittinghofer A, Ismail S (2016) PDE6d-mediated sorting of INPP5E into the cilium is determined by cargo-carrier affinity. Nat Commun 7: 11366.
36. Mondal MS, Wang Z, Seeds AM, Rando RR (2000) The specific binding of small molecule isoprenoids to rhoGDP dissociation inhibitor (rhoGDI). Biochemistry 39(2): 406-412.
37. Chelsky D, Ruskin B, Koshland DE, Jr (1985) Methyl-esterified proteins in a mammalian cell line. Biochemistry 24(23): 6651-6658.
38. Roy MO, Leventis R, Silvius JR (2000) Mutational and biochemical analysis of plasma membrane targeting mediated by the farnesylated, polybasic carboxy terminus of K-ras4B. Biochemistry 39(28): 8298-8307.
39. Bivona TG, et al. (2006) PKC regulates a farnesyl-electrostatic switch on K-Ras that promotes its association with Bcl-XL on mitochondria and induces apoptosis. Mol Cell 21(4): 481-493.
40. Wang MT, et al. (2015) K-Ras Promotes Tumorigenicity through Suppression of Noncanonical Wnt Signaling. Cell 163(5): 1237-1251.
41. Johnson L, et al. (1997) K-ras is an essential gene in the mouse with partial functional overlap with N-ras. Genes Dev 11(19): 2468-2481.
42. Plowman SJ, et al. (2003) While K-ras is essential for mouse development, expression of the K-ras 4A splice variant is dispensable. Mol Cell Biol 23(24): 9245-9250.
43. Zhang H, et al. (2007) Deletion of PrBP/delta impedes transport of GRK1 and PDE6 catalytic subunits to photoreceptor outer segments. Proc Natl Acad Sci USA 104(21): 8857-8862.
44. Gillette WK, et al. (2015) Farnesylated and methylated KRAS4b: High yield production of protein suitable for biophysical studies of prenylated protein-lipid interactions. Sci Rep 5: 15916.
45. Kabsch W (2010) Xds. Acta Crystallogr D Biol Crystallogr 66(Pt 2): 125-132.
46. McCoy AJ, et al. (2007) Phaser crystallographic software. J Appl Cryst 40(Pt 4): 658-674.
47. Emsley P, Lohkamp B, Scott WG, Cowtan K (2010) Features and development of Coot. Acta Crystallogr D Biol Crystallogr 66(Pt 4): 486-501.
48. Adams PD, et al. (2010) PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66(Pt 2): 213-221.
49. Afonine PV, et al. (2012) Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr D Biol Crystallogr 68(Pt 4): 352-367.
50. Murshudov GN, et al. (2011) REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr D Biol Crystallogr 67(Pt 4): 355-367.
51. Krissinel E, Henrick K (2004) Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr D Biol Crystallogr 60(Pt 12): 2256-2268.
52. Schrodinger, LLC (2015) The PyMOL Molecular Graphics System, Version 1.8 (Schrodinger, LLC, New York).
53. Morin A, et al. (2013) Collaboration gets the most out of software. eLife 2: E01456.
54. Zhao H, Brautigam CA, Ghirlando R, Schuck P (2013) Overview of current methods in sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation. Curr Protoc Protein Sci 20: 20.12.
55. Zhao H, et al. (2013) Recorded scan times can limit the accuracy of sedimentation coefficients in analytical ultracentrifugation. Anal Biochem 437(1): 104-108.
56. Schuck P (2000) Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and lamm equation modeling. Biophys J 78(3): 1606-1619.
57. Cole JL, Lary JW, P Moody T, Laue TM (2008) Analytical ultracentrifugation: Sedimentation velocity and sedimentation equilibrium. Methods Cell Biol 84: 143-179.
58. Pace CN, Vajdos F, Fee L, Grimsley G, Gray T (1995) How to measure and predict the molar absorption coefficient of a protein. Protein Sci 4(11): 2411-2423.
59. Zhao H, Brown PH, Schuck P (2011) On the distribution of protein refractive index increments. Biophys J 100(9): 2309-2317.
60. Zhao H, Schuck P (2015) Combining biophysical methods for the analysis of protein complex stoichiometry and affinity in SEDPHAT. Acta Crystallogr D Biol Crystallogr 71(Pt 1): 3-14.
61. Johnson ML (1992) Why, when, and how biochemists should use least squares. Anal Biochem 206(2): 215-225.