Publications:
Autoantibody and hormone activation of the thyrotropin G protein-coupled receptor. Faust B, Billesboelle CB, Singh I, Zhang K, Hoppe N, Pinto AFM, Muftuoglu YM, Billesboelle CB, Saghatelian A, Cheng Y#, Manglik A#. bioRxiv. 2022. #Corresponding Authors
Selective G protein signaling driven by substance P–neurokinin receptor dynamics. Harris JA*, Faust B*, Gondin BA*, Dämgen MA, Suomivuori C, Veldhius NA, Cheng Y#, Dror RO#, Thal DM#, Manglik A#. Nature Chemical Biology. 2022; 18:109-115. *Equal contribution #Corresponding Authors
Biochemical Assays to Directly Assess Smoothened Activation by a Conformationally Sensitive Nanobody. Deshpande I, Manglik A. Methods in Molecular Biology. 2022;2374:149-60.
Universal Polymerase Chain Reaction and Antibody Testing Demonstrate Little to No Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in a Rural Community. Appa A, Takahashi S, Rodriguez-Barraquer I, Chamie G, Sawyer A, Duarte E, Hakim J, Turcios K, Vinden J, Janson O, Manglik A, Peluso MJ, Deeks SG, Henrich TJ, Torres L, Rodgers M, Hackett J, Chiu C, Havlir D, Greenhouse B. Open Forum in Infectious Diseases. 2021;8(1):ofaa531.
CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes. Gupta M, Azumaya CM, Moritz M, Pourmal S, Diallo A, Merz GE, Jang G, Bouhaddou M, Fossati A, Brilot AF, Diwanji D, Hernandez E, Herrera N, Kratochvil HT, Lam VL, Li F, Li Y, Nguyen HC, Nowotny C, Owens TW, Peters JK, Rizo AN, Schulze-Gahmen U, Smith AM, Young ID, Yu Z, Asarnow D, Billesbolle C, Campbell MG, Chen J, Chen KH, Chio US, Dickinson MS, Doan L, Jin M, Kim K, Li J, Li YL, Linossi E, Liu Y, Lo M, Lopez J, Lopez KE, Mancino A, Moss FR, Paul MD, Pawar KI, Pelin A, Pospiech TH, Puchades C, Remesh SG, Safari M, Schaefer K, Sun M, Tabios MC, Thwin AC, Titus EW, Trenker R, Tse E, Tsui TKM, Wang F, Zhang K, Zhang Y, Zhao J, Zhou F, Zhou Y, Zuliani-Alvarez L, Consortium QSB, Agard DA, Cheng Y, Fraser JS, Jura N, Kortemme T, Manglik A, Southworth DR, Stroud RM, Swaney DL, Krogan NJ, Frost A, Rosenberg OS, Verba KA. bioRxiv. 2021.
Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia. Asarnow D*, Wang B*, Lee WH, Hu Y, Huang CW, Faust B, Ng PML, Ngoh EZX, Bohn M, Bulkley D, Pizzorno A, Ary B, Tan HC, Lee CY, Minhat RA, Terrier O, Soh MK, Teo FJ, Yeap YYC, Seah SGK, Chan CEZ, Connelly E, Young NJ, Maurer-Stroh S, Renia L, Hanson BJ, Rosa-Calatrava M, Manglik A#, Cheng Y#, Craik CS#, Wang CI#. Cell. 2021;184(12):3192-204 e16. *Equal contribution #Corresponding Authors
Protein design and variant prediction using autoregressive generative models. Shin JE, Riesselman AJ, Kollasch AW, McMahon C, Simon E, Sander C, Manglik A, Kruse AC, Marks DS. Nature Communications. 2021;12(1):2403.
Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits. Arveseth CD, Happ JT, Hedeen DS, Zhu JF, Capener JL, Klatt Shaw D, Deshpande I, Liang J, Xu J, Stubben SL, Nelson IB, Walker MF, Kawakami K, Inoue A, Krogan NJ, Grunwald DJ, Huttenhain R, Manglik A, Myers BR. PLoS Biology. 2021;19(4):e3001191.
Surface Proteomics Reveals CD72 as a Target for In Vitro-Evolved Nanobody-Based CAR-T Cells in KMT2A/MLL1-Rearranged B-ALL. Nix MA, Mandal K, Geng H, Paranjape N, Lin YT, Rivera JM, Marcoulis M, White KL, Whitman JD, Bapat SP, Parker KR, Ramirez J, Deucher A, Phojanokong P, Steri V, Fattahi F, Hann BC, Satpathy AT, Manglik A, Stieglitz E, Wiita AP. Cancer Discovery. 2021;11(8):2032-49.
An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike. Schoof M*, Faust B*, Saunders RA*, Sangwan S*, Rezelj V*, Hoppe N, Boone M, Billesbolle CB, Puchades C, Azumaya CM, Kratochvil HT, Zimanyi M, Deshpande I, Liang J, Dickinson S, Nguyen HC, Chio CM, Merz GE, Thompson MC, Diwanji D, Schaefer K, Anand AA, Dobzinski N, Zha BS, Simoneau CR, Leon K, White KM, Chio US, Gupta M, Jin M, Li F, Liu Y, Zhang K, Bulkley D, Sun M, Smith AM, Rizo AN, Moss F, Brilot AF, Pourmal S, Trenker R, Pospiech T, Gupta S, Barsi-Rhyne B, Belyy V, Barile-Hill AW, Nock S, Liu Y, Krogan NJ, Ralston CY, Swaney DL, Garcia-Sastre A, Ott M, Vignuzzi M, Consortium QSB, Walter P#, Manglik A#. Science. 2020;370(6523):1473-9. *Equal contribution #Corresponding Authors
Hedgehog pathway activation through nanobody-mediated conformational blockade of the Patched sterol conduit. Zhang Y, Lu WJ, Bulkley DP, Liang J, Ralko A, Han S, Roberts KJ, Li A, Cho W, Cheng Y, Manglik A#, Beachy PA#. PNAS. 2020;117(46):28838-46. #Corresponding Authors
Bi-paratopic and multivalent VH domains block ACE2 binding and neutralize SARS-CoV-2. Bracken CJ, Lim SA, Solomon P, Rettko NJ, Nguyen DP, Zha BS, Schaefer K, Byrnes JR, Zhou J, Lui I, Liu J, Pance K, Consortium QSB, Zhou XX, Leung KK, Wells JA. Nature Chemical Biology. 2021;17(1):113-21.
Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, Jureka AS, Obernier K, Guo JZ, Batra J, Kaake RM, Weckstein AR, Owens TW, Gupta M, Pourmal S, Titus EW, Cakir M, Soucheray M, McGregor M, Cakir Z, Jang G, O'Meara MJ, Tummino TA, Zhang Z, Foussard H, Rojc A, Zhou Y, Kuchenov D, Huttenhain R, Xu J, Eckhardt M, Swaney DL, Fabius JM, Ummadi M, Tutuncuoglu B, Rathore U, Modak M, Haas P, Haas KM, Naing ZZC, Pulido EH, Shi Y, Barrio-Hernandez I, Memon D, Petsalaki E, Dunham A, Marrero MC, Burke D, Koh C, Vallet T, Silvas JA, Azumaya CM, Billesbolle C, Brilot AF, Campbell MG, Diallo A, Dickinson MS, Diwanji D, Herrera N, Hoppe N, Kratochvil HT, Liu Y, Merz GE, Moritz M, Nguyen HC, Nowotny C, Puchades C, Rizo AN, Schulze-Gahmen U, Smith AM, Sun M, Young ID, Zhao J, Asarnow D, Biel J, Bowen A, Braxton JR, Chen J, Chio CM, Chio US, Deshpande I, Doan L, Faust B, Flores S, Jin M, Kim K, Lam VL, Li F, Li J, Li YL, Li Y, Liu X, Lo M, Lopez KE, Melo AA, Moss FR, 3rd, Nguyen P, Paulino J, Pawar KI, Peters JK, Pospiech TH, Jr., Safari M, Sangwan S, Schaefer K, Thomas PV, Thwin AC, Trenker R, Tse E, Tsui TKM, Wang F, Whitis N, Yu Z, Zhang K, Zhang Y, Zhou F, Saltzberg D, Consortium QSB, Hodder AJ, Shun-Shion AS, Williams DM, White KM, Rosales R, Kehrer T, Miorin L, Moreno E, Patel AH, Rihn S, Khalid MM, Vallejo-Gracia A, Fozouni P, Simoneau CR, Roth TL, Wu D, Karim MA, Ghoussaini M, Dunham I, Berardi F, Weigang S, Chazal M, Park J, Logue J, McGrath M, Weston S, Haupt R, Hastie CJ, Elliott M, Brown F, Burness KA, Reid E, Dorward M, Johnson C, Wilkinson SG, Geyer A, Giesel DM, Baillie C, Raggett S, Leech H, Toth R, Goodman N, Keough KC, Lind AL, Zoonomia C, Klesh RJ, Hemphill KR, Carlson-Stevermer J, Oki J, Holden K, Maures T, Pollard KS, Sali A, Agard DA, Cheng Y, Fraser JS, Frost A, Jura N, Kortemme T, Manglik A, Southworth DR, Stroud RM, Alessi DR, Davies P, Frieman MB, Ideker T, Abate C, Jouvenet N, Kochs G, Shoichet B, Ott M, Palmarini M, Shokat KM, Garcia-Sastre A, Rassen JA, Grosse R, Rosenberg OS, Verba KA, Basler CF, Vignuzzi M, Peden AA, Beltrao P, Krogan NJ. Science. 2020;370(6521).
Test performance evaluation of SARS-CoV-2 serological assays. Whitman JD, Hiatt J, Mowery CT, Shy BR, Yu R, Yamamoto TN, Rathore U, Goldgof GM, Whitty C, Woo JM, Gallman AE, Miller TE, Levine AG, Nguyen DN, Bapat SP, Balcerek J, Bylsma SA, Lyons AM, Li S, Wong AW, Gillis-Buck EM, Steinhart ZB, Lee Y, Apathy R, Lipke MJ, Smith JA, Zheng T, Boothby IC, Isaza E, Chan J, Acenas DD, 2nd, Lee J, Macrae TA, Kyaw TS, Wu D, Ng DL, Gu W, York VA, Eskandarian HA, Callaway PC, Warrier L, Moreno ME, Levan J, Torres L, Farrington LA, Loudermilk RP, Koshal K, Zorn KC, Garcia-Beltran WF, Yang D, Astudillo MG, Bernstein BE, Gelfand JA, Ryan ET, Charles RC, Iafrate AJ, Lennerz JK, Miller S, Chiu CY, Stramer SL, Wilson MR, Manglik A, Ye CJ, Krogan NJ, Anderson MS, Cyster JG, Ernst JD, Wu AHB, Lynch KL, Bern C, Hsu PD, Marson A. Nature Biotechnology. 2020;38(10):1174-83.
Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. Billesbolle CB*, Azumaya CM*, Kretsch RC, Powers AS, Gonen S, Schneider S, Arvedson T, Dror RO, Cheng Y#, Manglik A#. Nature. 2020;586(7831):807-11. *Equal contribution #Corresponding Authors
β-Arrestin-Biased Angiotensin II Receptor Agonists for COVID-19. Manglik A, Wingler LM, Rockman HA, Lefkowitz RJ. Circulation. 2020;142(4):318-20.
Agonist-selective recruitment of engineered protein probes and of GRK2 by opioid receptors in living cells. Stoeber M, Jullie D, Li J, Chakraborty S, Majumdar S, Lambert NA, Manglik A, von Zastrow M. elife. 2020;9.
Molecular Basis of Opioid Action: From Structures to New Leads. Manglik A. Biological Psychiatry. 2020;87(1):6-14.
Smoothened stimulation by membrane sterols drives Hedgehog pathway activity. Deshpande I, Liang J, Hedeen D, Roberts KJ, Zhang Y, Ha B, Latorraca NR, Faust B, Dror RO, Beachy PA, Myers BR#, Manglik A#. Nature. 2019;571(7764):284-8. #Corresponding Authors
Development of an antibody fragment that stabilizes GPCR/G-protein complexes. Maeda S, Koehl A, Matile H, Hu H, Hilger D, Schertler GFX, Manglik A, Skiniotis G, Dawson RJP, Kobilka BK. Nature Communications. 2018;9(1):3712.
Measuring ligand efficacy at the µ-opioid receptor using a conformational biosensor. Livingston KE, Mahoney JP, Manglik A, Sunahara RK, Traynor JR. elife. 2018;7.
Structure of the µ-opioid receptor-Gi protein complex. Koehl A*, Hu H*, Maeda S, Zhang Y, Qu Q, Paggi JM, Latorraca NR, Hilger D, Dawson R, Matile H, Schertler GFX, Granier S, Weis WI, Dror RO, Manglik A#, Skiniotis G#, Kobilka BK#. Nature. 2018;558(7711):547-52. *Equal contribution #Corresponding Authors
A Genetically Encoded Biosensor Reveals Location Bias of Opioid Drug Action. Stoeber M, Jullie D, Lobingier BT, Laeremans T, Steyaert J, Schiller PW, Manglik A, von Zastrow M. Neuron. 2018;98(5):963-76 e5.
Sortase ligation enables homogeneous GPCR phosphorylation to reveal diversity in β-arrestin coupling. Staus DP, Wingler LM, Choi M, Pani B, Manglik A, Kruse AC, Lefkowitz RJ. PNAS. 2018;115(15):3834-9.
Yeast surface display platform for rapid discovery of conformationally selective nanobodies. McMahon C, Baier AS, Pascolutti R, Wegrecki M, Zheng S, Ong JX, Erlandson SC, Hilger D, Rasmussen SGF, Ring AM, Manglik A#, Kruse AC#. Nature Structural and Molecular Biology. 2018;25(3):289-96. #Corresponding Authors
Structural Basis for G Protein-Coupled Receptor Activation. Manglik A, Kruse AC. Biochemistry. 2017;56(42):5628-34.
Nanobodies to Study G Protein-Coupled Receptor Structure and Function. Manglik A, Kobilka BK, Steyaert J. Annual Reviews of Pharmacology and Toxicology. 2017;57:19-37.
Structure-based discovery of opioid analgesics with reduced side effects. Manglik A*, Lin H*, Aryal DK*, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hubner H, Huang XP, Sassano MF, Giguere PM, Lober S, Da D, Scherrer G, Kobilka BK#, Gmeiner P#, Roth BL#, Shoichet BK#. Nature. 2016;537(7619):185-90. *Equal contribution #Corresponding Authors
Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation. Staus DP*, Strachan RT*, Manglik A*, Pani B, Kahsai AW, Kim TH, Wingler LM, Ahn S, Chatterjee A, Masoudi A, Kruse AC, Pardon E, Steyaert J, Weis WI, Prosser RS, Kobilka BK#, Costa T#, Lefkowitz RJ#. Nature. 2016;535(7612):448-52. *Equal contribution #Corresponding Authors
Allosteric coupling from G protein to the agonist-binding pocket in GPCRs. DeVree BT, Mahoney JP, Velez-Ruiz GA, Rasmussen SG, Kuszak AJ, Edwald E, Fung JJ, Manglik A, Masureel M, Du Y, Matt RA, Pardon E, Steyaert J, Kobilka BK, Sunahara RK. Nature. 2016;535(7610):182-6.
Crystal structure of the human σ1 receptor. Schmidt HR, Zheng S, Gurpinar E, Koehl A, Manglik A, Kruse AC. Nature. 2016;532(7600):527-30.
High-density grids for efficient data collection from multiple crystals. Baxter EL, Aguila L, Alonso-Mori R, Barnes CO, Bonagura CA, Brehmer W, Brunger AT, Calero G, Caradoc-Davies TT, Chatterjee R, Degrado WF, Fraser JS, Ibrahim M, Kern J, Kobilka BK, Kruse AC, Larsson KM, Lemke HT, Lyubimov AY, Manglik A, McPhillips SE, Norgren E, Pang SS, Soltis SM, Song J, Thomaston J, Tsai Y, Weis WI, Woldeyes RA, Yachandra V, Yano J, Zouni A, Cohen AE. Acta Crystallogr D Struct Biol. 2016;72(Pt 1):2-11.
Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging. Maute RL, Gordon SR, Mayer AT, McCracken MN, Natarajan A, Ring NG, Kimura R, Tsai JM, Manglik A, Kruse AC, Gambhir SS, Weissman IL, Ring AM. PNAS. 2015;112(47):E6506-14.
Structural insights into µ-opioid receptor activation. Huang W*, Manglik A*#, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, Kato HE, Livingston KE, Thorsen TS, Kling RC, Granier S, Gmeiner P, Husbands SM, Traynor JR, Weis WI, Steyaert J, Dror RO, Kobilka BK#. Nature. 2015;524(7565):315-21. *Equal contribution #Corresponding Authors
Propagation of conformational changes during µ-opioid receptor activation. Sounier R, Mas C, Steyaert J, Laeremans T, Manglik A, Huang W, Kobilka BK, Demene H, Granier S. Nature. 2015;524(7565):375-8.
Structural basis for nucleotide exchange in heterotrimeric G proteins. Dror RO, Mildorf TJ, Hilger D, Manglik A, Borhani DW, Arlow DH, Philippsen A, Villanueva N, Yang Z, Lerch MT, Hubbell WL, Kobilka BK, Sunahara RK, Shaw DE. Science. 2015;348(6241):1361-5.
Structural Insights into the Dynamic Process of β2-Adrenergic Receptor Signaling. Manglik A*, Kim TH*, Masureel M, Altenbach C, Yang Z, Hilger D, Lerch MT, Kobilka TS, Thian FS, Hubbell WL#, Prosser RS#, Kobilka BK#. Cell. 2015;161(5):1101-11. *Equal contribution #Corresponding Authors
A comparison of chemical shift sensitivity of trifluoromethyl tags: optimizing resolution in 19F NMR studies of proteins. Ye L, Larda ST, Frank Li YF, Manglik A, Prosser RS. Journal of Biomolecular NMR. 2015;62(1):97-103.
G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors. Li L, Homan KT, Vishnivetskiy SA, Manglik A, Tesmer JJ, Gurevich VV, Gurevich EV. Journal of Biological Chemistry. 2015;290(17):10775-90.
Goniometer-based femtosecond crystallography with X-ray free electron lasers. Cohen AE, Soltis SM, Gonzalez A, Aguila L, Alonso-Mori R, Barnes CO, Baxter EL, Brehmer W, Brewster AS, Brunger AT, Calero G, Chang JF, Chollet M, Ehrensberger P, Eriksson TL, Feng Y, Hattne J, Hedman B, Hollenbeck M, Holton JM, Keable S, Kobilka BK, Kovaleva EG, Kruse AC, Lemke HT, Lin G, Lyubimov AY, Manglik A, Mathews, II, McPhillips SE, Nelson S, Peters JW, Sauter NK, Smith CA, Song J, Stevenson HP, Tsai Y, Uervirojnangkoorn M, Vinetsky V, Wakatsuki S, Weis WI, Zadvornyy OA, Zeldin OB, Zhu D, Hodgson KO. PNAS. 2014;111(48):17122-7.
Covalent agonists for studying G protein-coupled receptor activation. Weichert D, Kruse AC, Manglik A, Hiller C, Zhang C, Hubner H, Kobilka BK, Gmeiner P. PNAS. 2014;111(29):10744-8.
The role of protein dynamics in GPCR function: insights from the β2AR and rhodopsin. Manglik A, Kobilka B. Current Opinions in Cell Biology. 2014;27:136-43.
Activation and allosteric modulation of a muscarinic acetylcholine receptor. Kruse AC*, Ring AM*, Manglik A, Hu J, Hu K, Eitel K, Hubner H, Pardon E, Valant C, Sexton PM, Christopoulos A, Felder CC, Gmeiner P, Steyaert J, Weis WI, Garcia KC, Wess J, Kobilka BK. Nature. 2013;504(7478):101-6. *Equal contribution
Applications of molecular replacement to G protein-coupled receptors. Kruse AC, Manglik A, Kobilka BK, Weis WI. Acta Crystallogr D Biol Crystallogr. 2013;69(Pt 11):2287-92.
Adrenaline-activated structure of β2-adrenoceptor stabilized by an engineered nanobody. Ring AM*, Manglik A*, Kruse AC*, Enos MD, Weis WI, Garcia KC#, Kobilka BK#. Nature. 2013;502(7472):575-9. *Equal contribution #Corresponding Authors
The role of ligands on the equilibria between functional states of a G protein-coupled receptor. Kim TH, Chung KY, Manglik A, Hansen AL, Dror RO, Mildorf TJ, Shaw DE, Kobilka BK, Prosser RS. JACS. 2013;135(25):9465-74.
Structure of active β-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide. Shukla AK*, Manglik A*, Kruse AC*, Xiao K, Reis RI, Tseng WC, Staus DP, Hilger D, Uysal S, Huang LY, Paduch M, Tripathi-Shukla P, Koide A, Koide S, Weis WI, Kossiakoff AA, Kobilka BK#, Lefkowitz RJ#. Nature. 2013;497(7447):137-41.
The dynamic process of β2-adrenergic receptor activation. Nygaard R, Zou Y, Dror RO, Mildorf TJ, Arlow DH, Manglik A, Pan AC, Liu CW, Fung JJ, Bokoch MP, Thian FS, Kobilka TS, Shaw DE, Mueller L, Prosser RS, Kobilka BK. Cell. 2013;152(3):532-42.
Role of detergents in conformational exchange of a G protein-coupled receptor. Chung KY, Kim TH, Manglik A, Alvares R, Kobilka BK, Prosser RS. Journal of Biological Chemistry. 2012;287(43):36305-11.
A new class of amphiphiles bearing rigid hydrophobic groups for solubilization and stabilization of membrane proteins. Chae PS, Rasmussen SG, Rana RR, Gotfryd K, Kruse AC, Manglik A, Cho KH, Nurva S, Gether U, Guan L, Loland CJ, Byrne B, Kobilka BK, Gellman SH. Chemistry. 2012;18(31):9485-90.
Structure of the delta-opioid receptor bound to naltrindole. Granier S, Manglik A*, Kruse AC*, Kobilka TS, Thian FS, Weis WI, Kobilka BK. Nature. 2012;485(7398):400-4.
Crystal structure of the µ-opioid receptor bound to a morphinan antagonist. Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S. Nature. 2012;485(7398):321-6.
Stably integrated luxCDABE for assessment of Salmonella invasion kinetics. Flentie KN, Qi M, Gammon ST, Razia Y, Lui F, Marpegan L, Manglik A, Piwnica-Worms D, McKinney JS. Molecular Imaging. 2008;7(5):222-33.