MBPH Faculty

Raymond Stevens, PhD
Raymond Stevens, PhD
Provost Professor of Biological Sciences and Chemistry / Director, The Bridge@USC
Broad CIRM Center
University Park Campus, MCB 309 University Park Campus Los Angeles
My research has been focused on understanding the structure and function of biological macromolecules in the human body for over 20 years, with a particular focus on human G protein-coupled receptor (GPCR) research since the early 1990’s. After 17 years of effort, including technology developments in protein crystallography robotics for structural biology research on membrane proteins, in 2007 we solved the crystal structure of the human ß2-adrenergic receptor bound to the partial inverse agonist carazolol at 2.4 Å which was a Science Magazine “Breakthrough of the Year” candidate. Since that time, we have solved more than 20 distinct GPCR structures and more than 34 complexes including receptors from the rhodopsin (adrenergic, adenosine, dopamine, sphingolipid, opioids, purinergic, histamine, cannabinoid, chemokine, angiotensin), secretin (glucagon), glutamate (mGluR1) and frizzled (smoothened) families. Our highest resolution structures of the delta opioid and A2A adenosine receptor at 1.8 Å have shed new light into the allosteric control of GPCRs by sodium and cholesterol. Our research program is focused on understanding the structural diversity among the GPCR family, as well as technology development necessary to understand mechanisms of signal transduction and coupling of GPCRs with their partners, including G proteins, GPCR kinases, and arrestin. In combination with the crystallographic studies, we have collaborated with key leaders in the field to use NMR, HDX, and EM techniques, as well as pharmacology, biochemistry, chemistry, and biology studies to provide insight into the molecular mechanisms of this important protein family. As part of a larger collaborative program, we strive to collectively realize a dynamic, atomic-level model of the human body to accelerate the creation and implementation of novel therapies and cures for a host of heretofore intractable diseases and conditions.

Accelerating the Throughput of Affinity Mass Spectrometry-Based Ligand Screening toward a G Protein-Coupled Receptor Anal Chem. 2019 Jul 02; 91(13):8162-8169. . View in PubMed

A Single Reactive Noncanonical Amino Acid Is Able to Dramatically Stabilize Protein Structure ACS Chem Biol. 2019 Jun 21; 14(6):1150-1153. . View in PubMed

Advancing Chemokine GPCR Structure Based Drug Discovery Structure. 2019 Mar 05; 27(3):405-408. . View in PubMed

An online resource for GPCR structure determination and analysis Nat Methods. 2019 Feb; 16(2):151-162. . View in PubMed

Crystal Structure of the Human Cannabinoid Receptor CB2Cell. 2019 Jan 24; 176(3):459-467. e13. . View in PubMed

Crystal Structure of the Human Cannabinoid Receptor CB2 Cell. 2019 Jan 10. . View in PubMed

Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptor Nat Chem Biol. 2019 01; 15(1):11-17. . View in PubMed

Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptor Nat Chem Biol. 2019 Jan; 15(1):11-17. . View in PubMed

A2A adenosine receptor functional states characterized by 19F-NMR Proc Natl Acad Sci U S A. 2018 Nov 21. . View in PubMed

Crystal structure of the Frizzled 4 receptor in a ligand-free state Nature. 2018 Aug; 560(7720):666-670. . View in PubMed

Author Correction: Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2Y1 and P2Y12 receptors Sci Rep. 2018 Jul 24; 8(1):11380. . View in PubMed

Computational design of thermostabilizing point mutations for G protein-coupled receptors Elife. 2018 Jun 21; 7. . View in PubMed

Chemical Diversity in the G Protein-Coupled Receptor Superfamily Trends Pharmacol Sci. 2018 May; 39(5):494-512. . View in PubMed

5-HT2C Receptor Structures Reveal the Structural Basis of GPCR PolypharmacologyCell. 2018 Feb 08; 172(4):719-730. e14. . View in PubMed

Allosteric Coupling of Drug Binding and Intracellular Signaling in the A2A Adenosine ReceptorCell. 2018 Jan 11; 172(1-2):68-80. e12. . View in PubMed

Crystal structure of the Frizzled 4 receptor in a ligand-free state Nature. 2018 08; 560(7720):666-670. . View in PubMed

Chemical Diversity in the G Protein-Coupled Receptor Superfamily Trends Pharmacol Sci. 2018 05; 39(5):494-512. . View in PubMed

A2A adenosine receptor functional states characterized by 19F-NMR Proc Natl Acad Sci U S A. 2018 12 11; 115(50):12733-12738. . View in PubMed

Computational design of thermostabilizing point mutations for G protein-coupled receptors Elife. 2018 06 21; 7. . View in PubMed

Allosteric Coupling of Drug Binding and Intracellular Signaling in the A2A Adenosine ReceptorCell. 2018 01 11; 172(1-2):68-80. e12. . View in PubMed

5-HT2C Receptor Structures Reveal the Structural Basis of GPCR PolypharmacologyCell. 2018 02 08; 172(4):719-730. e14. . View in PubMed

A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor Medchemcomm. 2017 Jun 01; 8(6):1332-1336. . View in PubMed

Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand Nat Commun. 2017 May 17; 8:15383. . View in PubMed

Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand Nat Commun. 2017 05 17; 8:15383. . View in PubMed

Crystal Structure of the Human Cannabinoid Receptor CB1Cell. 2016 Oct 20; 167(3):750-762. e14. . View in PubMed

An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction channels Nat Commun. 2016 Jan 12; 7:8770. . View in PubMed

Conformational states of the full-length glucagon receptor Nat Commun. 2015 Jul 31; 6:7859. . View in PubMed

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser Nature. 2015 Jul 30; 523(7562):561-7. . View in PubMed

Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1 Cell. 2015 Jun 18; 161(7):1633-43. . View in PubMed

Constitutive phospholipid scramblase activity of a G protein-coupled receptor Nat Commun. 2014 Oct 08; 5:5115. . View in PubMed

Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges Structure. 2014 Aug 05; 22(8):1120-1139. . View in PubMed

Allosteric sodium in class A GPCR signaling Trends Biochem Sci. 2014 May; 39(5):233-44. . View in PubMed

Agonist-bound structure of the human P2Y12 receptor Nature. 2014 May 01; 509(7498):119-22. . View in PubMed

J Biol Chem. 2013 Nov 29; 288(48):34470-83. . View in PubMed

Asia growth in membrane protein structure Curr Opin Struct Biol. 2013 Aug; 23(4):481-2. . View in PubMed

Coordinating the impact of structural genomics on the human a-helical transmembrane proteome Nat Struct Mol Biol. 2013 Feb; 20(2):135-8. . View in PubMed

A novel approach to quantify G-protein-coupled receptor dimerization equilibrium using bioluminescence resonance energy transfer Methods Mol Biol. 2013; 1013:93-127. . View in PubMed

Crystal structure of a voltage-gated K+ channel pore module in a closed state in lipid membranes J Biol Chem. 2012 Dec 14; 287(51):43063-70. . View in PubMed

Agonists for 13 trace amine-associated receptors provide insight into the molecular basis of odor selectivity ACS Chem Biol. 2012 Jul 20; 7(7):1184-9. . View in PubMed

Biased signaling pathways in ß2-adrenergic receptor characterized by 19F-NMR Science. 2012 Mar 02; 335(6072):1106-10. . View in PubMed

Crystal structure of a lipid G protein-coupled receptor Science. 2012 Feb 17; 335(6070):851-5. . View in PubMed

Chaperone-like therapy with tetrahydrobiopterin in clinical trials for phenylketonuria: is genotype a predictor of response? JIMD Rep. 2012; 5:59-70.. View in PubMed

A roadmap to membrane protein structures Methods. 2011 Dec; 55(4):271-2. . View in PubMed

Conserved binding mode of human beta2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography J Am Chem Soc. 2010 Aug 25; 132(33):11443-5. . View in PubMed

Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: discovery of a deacylating water molecule and insight into enzyme inactivation J Mol Biol. 2010 Jul 23; 400(4):743-54. . View in PubMed

Crystal structure of the botulinum neurotoxin type G binding domain: insight into cell surface binding J Mol Biol. 2010 Apr 16; 397(5):1287-97. . View in PubMed

A single-domain llama antibody potently inhibits the enzymatic activity of botulinum neurotoxin by binding to the non-catalytic alpha-exosite binding region J Mol Biol. 2010 Apr 09; 397(4):1106-18. . View in PubMed

Converting an injectable protein therapeutic into an oral form: phenylalanine ammonia lyase for phenylketonuria Mol Genet Metab. 2010 Jan; 99(1):4-9. . View in PubMed

Binding and inactivation mechanism of a humanized fatty acid amide hydrolase by alpha-ketoheterocycle inhibitors revealed from cocrystal structures J Am Chem Soc. 2009 Aug 05; 131(30):10497-506. . View in PubMed

Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008 Nat Rev Drug Discov. 2009 06; 8(6):455-63. . View in PubMed

Correlation of inhibitor effects on enzyme activity and thermal stability for the integral membrane protein fatty acid amide hydrolase Bioorg Med Chem Lett. 2008 Nov 15; 18(22):5847-50. . View in PubMed

Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications Nature. 2008 Nov 06; 456(7218):121-4. . View in PubMed

Crystal structure of botulinum neurotoxin type A in complex with the cell surface co-receptor GT1b-insight into the toxin-neuron interaction PLoS Pathog. 2008 Aug 15; 4(8):e1000129. . View in PubMed

A specific cholesterol binding site is established by the 28 A structure of the human beta2-adrenergic receptor. Structure. 2008 Jun; 16(6):897-905. . View in PubMed

Biophysical and ion channel functional characterization of the Torpedo californica nicotinic acetylcholine receptor in varying detergent-lipid environments J Membr Biol. 2008 May; 223(1):13-26. . View in PubMed

Crystal structure and DNA binding of the homeodomain of the stem cell transcription factor Nanog J Mol Biol. 2008 Feb 22; 376(3):758-70. . View in PubMed

Crystal structure of 2-keto-3-deoxygluconate kinase (TM0067) from Thermotoga maritima at 205 A resolution. Proteins. 2008 Feb 01; 70(2):603-8. . View in PubMed

Crystal structure of a monomeric form of severe acute respiratory syndrome coronavirus endonuclease nsp15 suggests a role for hexamerization as an allosteric switch J Virol. 2007 Jun; 81(12):6700-8. . View in PubMed

Crystal structure of an ORFan protein (TM1622) from Thermotoga maritima at 175 A resolution reveals a fold similar to the Ran-binding protein Mog1p. Proteins. 2006 Nov 15; 65(3):777-82. . View in PubMed

Comparative structural analysis of a novel glutathioneS-transferase (ATU5508) from Agrobacterium tumefaciens at 20 A resolution. Proteins. 2006 Nov 15; 65(3):527-37. . View in PubMed

Crystal structure of 2-phosphosulfolactate phosphatase (ComB) from Clostridium acetobutylicum at 26 A resolution reveals a new fold with a novel active site. Proteins. 2006 Nov 15; 65(3):771-6. . View in PubMed

Crystal structure of phosphoribosylformyl-glycinamidine synthase II, PurS subunit (TM1244) from Thermotoga maritima at 190 A resolution. Proteins. 2006 Oct 01; 65(1):249-54. . View in PubMed

Crystal structure of a glycerate kinase (TM1585) from Thermotoga maritima at 270 A resolution reveals a new fold. Proteins. 2006 Oct 01; 65(1):243-8. . View in PubMed

A structural perspective of the sequence variability within botulinum neurotoxin subtypes A1-A4 J Mol Biol. 2006 Sep 29; 362(4):733-42. . View in PubMed

Crystal structure of the ApbE protein (TM1553) from Thermotoga maritima at 158 A resolution. Proteins. 2006 Sep 01; 64(4):1083-90. . View in PubMed

Crystal structure of acireductone dioxygenase (ARD) from Mus musculus at 206 angstrom resolution. Proteins. 2006 Aug 15; 64(3):808-13. . View in PubMed

Crystal structure of nonstructural protein 10 from the severe acute respiratory syndrome coronavirus reveals a novel fold with two zinc-binding motifs J Virol. 2006 Aug; 80(16):7894-901. . View in PubMed

Crystal structure of phosphoribosylformylglycinamidine synthase II (smPurL) from Thermotoga maritima at 215 A resolution. Proteins. 2006 Jun 01; 63(4):1106-11. . View in PubMed

Crystal structure of TM1367 from Thermotoga maritima at 190 A resolution reveals an atypical member of the cyclophilin (peptidylprolyl isomerase) fold. Proteins. 2006 Jun 01; 63(4):1112-8. . View in PubMed

Crystal structure of a single-stranded DNA-binding protein (TM0604) from Thermotoga maritima at 260 A resolution. Proteins. 2006 Apr 01; 63(1):256-60. . View in PubMed

Crystal structure of a conserved hypothetical protein (gi: 13879369) from Mouse at 190 A resolution reveals a new fold. Proteins. 2005 Dec 01; 61(4):1132-6. . View in PubMed

Crystal structure of Hsp33 chaperone (TM1394) from Thermotoga maritima at 220 A resolution. Proteins. 2005 Nov 15; 61(3):669-73. . View in PubMed

Crystal structure of a putative modulator of DNA gyrase (pmbA) from Thermotoga maritima at 195 A resolution reveals a new fold. Proteins. 2005 Nov 01; 61(2):444-8. . View in PubMed

Crystal structure of the global regulatory protein CsrA from Pseudomonas putida at 205 A resolution reveals a new fold. Proteins. 2005 Nov 01; 61(2):449-53. . View in PubMed

Crystal structure of an Apo mRNA decapping enzyme (DcpS) from Mouse at 183 A resolution. Proteins. 2005 Sep 01; 60(4):797-802. . View in PubMed

Crystal structure of botulinum neurotoxin type G light chain: serotype divergence in substrate recognition Biochemistry. 2005 Jul 19; 44(28):9574-80. . View in PubMed

Crystal structure of an indigoidine synthase A (IndA)-like protein (TM1464) from Thermotoga maritima at 190 A resolution reveals a new fold. Proteins. 2005 Jun 01; 59(4):864-8. . View in PubMed

Crystal structure of S-adenosylmethionine:tRNA ribosyltransferase-isomerase (QueA) from Thermotoga maritima at 20 A resolution reveals a new fold. Proteins. 2005 Jun 01; 59(4):869-74. . View in PubMed

Crystal structure of a formiminotetrahydrofolate cyclodeaminase (TM1560) from Thermotoga maritima at 280 A resolution reveals a new fold. Proteins. 2005 Mar 01; 58(4):976-81. . View in PubMed

Crystal structure of an alanine-glyoxylate aminotransferase from Anabaena spat 1. 70 A resolution reveals a noncovalently linked PLP cofactor. Proteins. 2005 Mar 01; 58(4):971-5. . View in PubMed

Crystal structure of an alpha/beta serine hydrolase (YDR428C) from Saccharomyces cerevisiae at 185 A resolution. Proteins. 2005 Feb 15; 58(3):755-8. . View in PubMed

Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations Proc Natl Acad Sci U S A. 2004 Nov 30; 101(48):16903-8. . View in PubMed

Crystal structure of a tandem cystathionine-beta-synthase (CBS) domain protein (TM0935) from Thermotoga maritima at 187 A resolution. Proteins. 2004 Oct 01; 57(1):213-7. . View in PubMed

Crystal structure of an allantoicase (YIR029W) from Saccharomyces cerevisiae at 24 A resolution. Proteins. 2004 Aug 15; 56(3):619-24. . View in PubMed

Crystal structure of a novel Thermotoga maritima enzyme (TM1112) from the cupin family at 183 A resolution. Proteins. 2004 Aug 15; 56(3):615-8. . View in PubMed

Crystal structure of a novel manganese-containing cupin (TM1459) from Thermotoga maritima at 165 A resolution. Proteins. 2004 Aug 15; 56(3):611-4. . View in PubMed

Crystal structure of an orphan protein (TM0875) from Thermotoga maritima at 200-A resolution reveals a new fold. Proteins. 2004 Aug 15; 56(3):607-10. . View in PubMed

Crystal structure of a putative NADPH-dependent oxidoreductase (GI: 18204011) from mouse at 210 A resolution. Proteins. 2004 Aug 15; 56(3):629-33. . View in PubMed

Crystal structure of a putative oxalate decarboxylase (TM1287) from Thermotoga maritima at 195 A resolution. Proteins. 2004 Aug 01; 56(2):392-5. . View in PubMed

Crystal structure of a methionine aminopeptidase (TM1478) from Thermotoga maritima at 19 A resolution. Proteins. 2004 Aug 01; 56(2):396-400. . View in PubMed

Crystal structure of a PIN (PilT N-terminus) domain (AF0591) from Archaeoglobus fulgidus at 190 A resolution. Proteins. 2004 Aug 01; 56(2):404-8. . View in PubMed

Crystal structure of O-acetylserine sulfhydrylase (TM0665) from Thermotoga maritima at 18 A resolution. Proteins. 2004 Aug 01; 56(2):387-91. . View in PubMed

A mass spectrometry plate reader: monitoring enzyme activity and inhibition with a Desorption/Ionization on Silicon (DIOS) platform Chembiochem. 2004 Jul 05; 5(7):921-7. . View in PubMed

Crystal structure of a ribose-5-phosphate isomerase RpiB (TM1080) from Thermotoga maritima at 190 A resolution. Proteins. 2004 Jul 01; 56(1):171-5. . View in PubMed

Crystal structure of a glycerophosphodiester phosphodiesterase (GDPD) from Thermotoga maritima (TM1621) at 160 A resolution. Proteins. 2004 Jul 01; 56(1):167-70. . View in PubMed

Crystal structure of an Udp-n-acetylmuramate-alanine ligase MurC (TM0231) from Thermotoga maritima at 23 A resolution. Proteins. 2004 Jun 01; 55(4):1078-81. . View in PubMed

Crystal structure of a type II quinolic acid phosphoribosyltransferase (TM1645) from Thermotoga maritima at 250 A resolution. Proteins. 2004 May 15; 55(3):768-71. . View in PubMed

Crystal structure of an aspartate aminotransferase (TM1255) from Thermotoga maritima at 190 A resolution. Proteins. 2004 May 15; 55(3):759-63. . View in PubMed

Crystal structure of a phosphoribosylaminoimidazole mutase PurE (TM0446) from Thermotoga maritima at 177-A resolution. Proteins. 2004 May 01; 55(2):474-8. . View in PubMed

Automated sample mounting and alignment system for biological crystallography at a synchrotron source Structure. 2004 Apr; 12(4):537-45. . View in PubMed

Crystal structure of a putative PII-like signaling protein (TM0021) from Thermotoga maritima at 25 A resolution. Proteins. 2004 Mar 01; 54(4):810-3. . View in PubMed

Crystal structure of an HEPN domain protein (TM0613) from Thermotoga maritima at 175 A resolution. Proteins. 2004 Mar 01; 54(4):806-9. . View in PubMed

Crystal structure of a putative glutamine amido transferase (TM1158) from Thermotoga maritima at 17 A resolution. Proteins. 2004 Mar 01; 54(4):801-5. . View in PubMed

Crystal structure of an iron-containing 1,3-propanediol dehydrogenase (TM0920) from Thermotoga maritima at 13 A resolution. Proteins. 2004 Jan 01; 54(1):174-7. . View in PubMed

Biopterin responsive phenylalanine hydroxylase deficiency Genet Med. 2004 Jan-Feb; 6(1):27-32. . View in PubMed

Crystal structure of gamma-glutamyl phosphate reductase (TM0293) from Thermotoga maritima at 20 A resolution. Proteins. 2004 Jan 01; 54(1):157-61. . View in PubMed

A fully integrated protein crystallization platform for small-molecule drug discovery J Struct Biol. 2003 Apr; 142(1):207-17. . View in PubMed

Crystal structure of a zinc-containing glycerol dehydrogenase (TM0423) from Thermotoga maritima at 15 A resolution. Proteins. 2003 Feb 01; 50(2):371-4. . View in PubMed

Crystal structure of thy1, a thymidylate synthase complementing protein from Thermotoga maritima at 225 A resolution. Proteins. 2002 Oct 01; 49(1):142-5. . View in PubMed

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