Integrating energy calculations with functional assays to decipher the specificity of G protein-RGS protein interactions

Nature Structural and Molecular Biology

Volumn 18, Issue 7, 2011, Pages 846-853

  Kosloff, Mickey ^a   Travis, Amanda M ^a   Bosch, Dustin E ^b   Siderovski, David P ^b   Arshavsky, Vadim Y ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COLICIN; COLICIN E7; GUANINE NUCLEOTIDE BINDING PROTEIN; GUANOSINE TRIPHOSPHATASE; PROTEIN RGS16; RGS PROTEIN; RGS4 PROTEIN; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ARTICLE; BINDING AFFINITY; CRYSTAL STRUCTURE; ENZYME ACTIVITY; MOLECULAR RECOGNITION; MUTAGENESIS; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; SEQUENCE ALIGNMENT;

AMINO ACID SEQUENCE; BINDING SITES; COLICINS; GTP-BINDING PROTEINS; HUMANS; MOLECULAR SEQUENCE DATA; MUTAGENESIS, SITE-DIRECTED; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN INTERACTION MAPPING; PROTEIN STRUCTURE, TERTIARY; RGS PROTEINS; SEQUENCE ALIGNMENT; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 79960064354     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.2068     Document Type: Article

References (60)

1. Siderovski, D.P., Hessel, A., Chung, S., Mak, T.W. & Tyers, M. A new family of regulators of G-protein-coupled receptors? Curr. Biol. 6, 211-212 (1996).
2. Koelle, M.R. & Horvitz, H.R. EGL-10 regulates G protein signaling in the C. elegans nervous system and shares a conserved domain with many mammalian proteins. Cell 84, 115-125 (1996). (Pubitemid 26031466)
3. Berman, D.M., Wikie, T.M. & Gilman, A.G. GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein α subunits. Cell 86, 445-452 (1996). (Pubitemid 26272084)
4. Hunt, T.W., Fields, T.A., Casey, P.J. & Peralta, E.G. RGS10 is a selective activator of Gαi GTPase activity. Nature 383, 175-177 (1996). (Pubitemid 26303981)
5. Watson, N., Linder, M.E., Druey, K.M., Kehrl, J.H. & Blumer, K.J. RGS family members: GTPase-activating proteins for heterotrimeric G-protein α-subunits. Nature 383, 172-175 (1996). (Pubitemid 26303980)
6. Ross, E.M. & Wilkie, T.M. GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu. Rev. Biochem. 69, 795-827 (2000).
7. Hollinger, S. & Hepler, J.R. Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol. Rev. 54, 527-559 (2002).
8. Neubig, R.R. & Siderovski, D.P. Regulators of G-protein signalling as new central nervous system drug targets. Nat. Rev. Drug Discov. 1, 187-197 (2002). (Pubitemid 37361422)
9. Neitzel, K.L. & Hepler, J.R. Cellular mechanisms that determine selective RGS protein regulation of G protein-coupled receptor signaling. Semin. Cell Dev. Biol. 17, 383-389 (2006). (Pubitemid 44066843)
10. Hurst, J.H. & Hooks, S.B. Regulator of G-protein signaling (RGS) proteins in cancer biology. Biochem. Pharmacol. 78, 1289-1297 (2009).
11. Wang, Q., Liu, M., Mullah, B., Siderovski, D.P. & Neubig, R.R. Receptor-selective effects of endogenous RGS3 and RGS5 to regulate mitogen-activated protein kinase activation in rat vascular smooth muscle cells. J. Biol. Chem. 277, 24949-24958 (2002). (Pubitemid 34951796)
12. Tang, K.M. et al. Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat. Med. 9, 1506-1512 (2003).
13. Xie, G.X. & Palmer, P.P. How regulators of G protein signaling achieve selective regulation. J. Mol. Biol. 366, 349-365 (2007). (Pubitemid 46136207)
14. Cifelli, C. et al. RGS4 regulates parasympathetic signaling and heart rate control in the sinoatrial node. Circ. Res. 103, 527-535 (2008).
15. Bansal, G., Druey, K.M. & Xie, Z. R4 RGS proteins: regulation of G-protein signaling and beyond. Pharmacol. Ther. 116, 473-495 (2007). (Pubitemid 350116944)
16. Bansal, G., Xie, Z., Rao, S., Nocka, K.H. & Druey, K.M. Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13. Nat. Immunol. 9, 73-80 (2008). (Pubitemid 350286206)
17. Laroche, G., Giguere, P.M., Roth, B.L., Trejo, J. & Siderovski, D.P. RNA interference screen for RGS protein specificity at muscarinic and protease-activated receptors reveals bidirectional modulation of signaling. Am. J. Physiol. Cell Physiol. 299, C654-C664 (2010).
18. Sowa, M.E. et al. Prediction and confirmation of a site critical for effector regulation of RGS domain activity. Nat. Struct. Biol. 8, 234-237 (2001). (Pubitemid 32180049)
19. Martemyanov, K.A. & Arshavsky, V.Y. Biology and functions of the RGS9 isoforms. Prog. Mol. Biol. Transl. Sci. 86, 205-227 (2009).
20. Skiba, N.P., Hopp, J.A. & Arshavsky, V.Y. The effector enzyme regulates the duration of G protein signaling in vertebrate photoreceptors by increasing the affinity between transducin and RGS protein. J. Biol. Chem. 275, 32716-32720 (2000).
21. Heximer, S.P., Watson, N., Linder, M.E., Blumer, K.J. & Hepler, J.R. RGS2/G0S8 is a selective inhibitor of Gqα function. Proc. Natl. Acad. Sci. USA 94, 14389-14393 (1997).
22. Heximer, S.P. et al. G protein selectivity is a determinant of RGS2 function. J. Biol. Chem. 274, 34253-34259 (1999). (Pubitemid 129511765)
23. Ingi, T. et al. Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity. J. Neurosci. 18, 7178-7188 (1998). (Pubitemid 28425805)
24. Tesmer, J.J., Berman, D.M., Gilman, A.G. & Sprang, S.R. Structure of RGS4 bound to AlF4-activated Giα1: stabilization of the transition state for GTP hydrolysis. Cell 89, 251-261 (1997). (Pubitemid 27199897)
25. Kimple, A.J. et al. Structural determinants of G-protein α subunit selectivity by regulator of G-protein signaling 2 (RGS2). J. Biol. Chem. 284, 19402-19411 (2009).
26. Slep, K.C. et al. Structural determinants for regulation of phosphodiesterase by a G protein at 2.0 A. Nature 409, 1071-1077 (2001). (Pubitemid 32204063)
27. Soundararajan, M. et al. Structural diversity in the RGS domain and its interaction with heterotrimeric G protein α-subunits. Proc. Natl. Acad. Sci. USA 105, 6457-6462 (2008). (Pubitemid 351758367)
28. Slep, K.C. et al. Molecular architecture of Gαo and the structural basis for RGS16-mediated deactivation. Proc. Natl. Acad. Sci. USA 105, 6243-6248 (2008). (Pubitemid 351758331)
29. Posner, B.A., Mukhopadhyay, S., Tesmer, J.J., Gilman, A.G. & Ross, E.M. Modulation of the affinity and selectivity of RGS protein interaction with G α subunits by a conserved asparagine/serine residue. Biochemistry 38, 7773-7779 (1999).
30. Kosloff, M. & Selinger, Z. GTPase catalysis by Ras and other G-proteins: insights from Substrate Directed SuperImposition. J. Mol. Biol. 331, 1157-1170 (2003). (Pubitemid 36969972)
31. Sprang, S.R., Chen, Z. & Du, X. Structural basis of effector regulation and signal termination in heterotrimeric Gα proteins. Adv. Protein Chem. 74, 1-65 (2007). (Pubitemid 47369746)
32. Sowa, M.E., He, W., Wensel, T.G. & Lichtarge, O. A regulator of G protein signaling interaction surface linked to effector specificity. Proc. Natl. Acad. Sci. USA 97, 1483-1488 (2000). (Pubitemid 30118467)
33. Siderovski, D.P. & Willard, F.S. The GAPs, GEFs, and GDIs of heterotrimeric G-protein α subunits. Int. J. Biol. Sci. 1, 51-66 (2005).
34. Sheinerman, F.B., Al-Lazikani, B. & Honig, B. Sequence, structure and energetic determinants of phosphopeptide selectivity of SH2 domains. J. Mol. Biol. 334, 823-841 (2003). (Pubitemid 37433895)
35. Sheinerman, F.B. & Honig, B. On the role of electrostatic interactions in the design of protein-protein interfaces. J. Mol. Biol. 318, 161-177 (2002). (Pubitemid 34729393)
36. Srinivasa, S.P., Watson, N., Overton, M.C. & Blumer, K.J. Mechanism of RGS4, a GTPase-activating protein for G protein α subunits. J. Biol. Chem. 273, 1529-1533 (1998). (Pubitemid 28133676)
37. Natochin, M., McEntaffer, R.L. & Artemyev, N.O. Mutational analysis of the Asn residue essential for RGS protein binding to G-proteins. J. Biol. Chem. 273, 6731-6735 (1998). (Pubitemid 28160333)
38. Wieland, T., Bahtijari, N., Zhou, X.B., Kleuss, C. & Simon, M.I. Polarity exchange at the interface of regulators of G protein signaling with G protein α-subunits. J. Biol. Chem. 275, 28500-28506 (2000).
39. Kortemme, T. & Baker, D. A simple physical model for binding energy hot spots in protein-protein complexes. Proc. Natl. Acad. Sci. USA 99, 14116-14121 (2002). (Pubitemid 35257634)
40. Ashkenazy, H., Erez, E., Martz, E., Pupko, T. & Ben-Tal, N. ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucleic Acids Res. 38, W529-W533 (2010).
41. Kühlmann, U.C., Pommer, A.J., Moore, G.R., James, R. & Kleanthous, C. Specificity in protein-protein interactions: the structural basis for dual recognition in endonuclease colicin-immunity protein complexes. J. Mol. Biol. 301, 1163-1178 (2000).
42. Schreiber, G. & Keating, A.E. Protein binding specificity versus promiscuity. Curr. Opin. Struct. Biol. 21, 50-61 (2010).
43. Kortemme, T. et al. Computational redesign of protein-protein interaction specificity. Nat. Struct. Mol. Biol. 11, 371-379 (2004). (Pubitemid 38436803)
44. Joachimiak, L.A., Kortemme, T., Stoddard, B.L. & Baker, D. Computational design of a new hydrogen bond network and at least a 300-fold specificity switch at a protein-protein interface. J. Mol. Biol. 361, 195-208 (2006). (Pubitemid 44041449)
45. Mandell, D.J. & Kortemme, T. Computer-aided design of functional protein interactions. Nat. Chem. Biol. 5, 797-807 (2009).
46. Levin, K.B. et al. Following evolutionary paths to protein-protein interactions with high affinity and selectivity. Nat. Struct. Mol. Biol. 16, 1049-1055 (2009).
47. Li, W. et al. Highly discriminating protein-protein interaction specificities in the context of a conserved binding energy hotspot. J. Mol. Biol. 337, 743-759 (2004). (Pubitemid 38326888)
48. Lippow, S.M., Wittrup, K.D. & Tidor, B. Computational design of antibody-affinity improvement beyond in vivo maturation. Nat. Biotechnol. 25, 1171-1176 (2007). (Pubitemid 47538113)
49. Skerker, J.M. et al. Rewiring the specificity of two-component signal transduction systems. Cell 133, 1043-1054 (2008). (Pubitemid 351787742)
50. Grigoryan, G., Reinke, A.W. & Keating, A.E. Design of protein-interaction specificity gives selective bZIP-binding peptides. Nature 458, 859-864 (2009).
51. Karanicolas, J. & Kuhlman, B. Computational design of affinity and specificity at protein-protein interfaces. Curr. Opin. Struct. Biol. 19, 458-463 (2009).
52. Edwards, A. Large-scale structural biology of the human proteome. Annu. Rev. Biochem. 78, 541-568 (2009).
53. Doudeva, L.G. et al. Crystal structural analysis and metal-dependent stability and activity studies of the ColE7 endonuclease domain in complex with DNA/Zn2+ or inhibitor/Ni2+. Protein Sci. 15, 269-280 (2006). (Pubitemid 43144999)
54. Ko, T.P., Liao, C.C., Ku, W.Y., Chak, K.F. & Yuan, H.S. The crystal structure of the DNase domain of colicin E7 in complex with its inhibitor Im7 protein. Structure 7, 91-102 (1999). (Pubitemid 29159185)
55. Huang, H. & Yuan, H.S. The conserved asparagine in the HNH motif serves an important structural role in metal finger endonucleases. J. Mol. Biol. 368, 812-821 (2007). (Pubitemid 46527620)
56. Petrey, D. et al. Using multiple structure alignments, fast model building, and energetic analysis in fold recognition and homology modeling. Proteins 53 (Suppl. 6) 430-435 (2003). (Pubitemid 37352202)
57. Xiang, Z. & Honig, B. Extending the accuracy limits of prediction for side-chain conformations. J. Mol. Biol. 311, 421-430 (2001). (Pubitemid 32744551)
58. MacKerell, A.D. et al. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 102, 3586-3616 (1998).
59. Honig, B. & Nicholls, A. Classical electrostatics in biology and chemistry. Science 268, 1144-1149 (1995).
60. Sridharan, S., Nicholls, A. & Honig, B. A new vertex algorithm to calculate solvent accessible surface areas. FASEB J. 6, A174 (1992).