Research Highlights

9BN7, X-ray crystal structure of TNFa-VNAR C4 complex
Ubah, O. C., Lake, E. W., Ott, K. L., Priyanka, S., Celeda, S., West, J. L., Gunaratne, G. S., Shi, K., Moeller, N. H., Porter, A. J., Aihara, H., Kosoff, D., LeBeau, A. M., and Barelle, C. J. (2025) The structural basis for the selective antagonism of soluble TNF-alpha by shark variable new antigen receptors. Nat Commun. 10.1038/s41467-025-66967-3
9ECY, Crystal structure of the SARS-CoV-2 NTD-targeted neutralizing antibody WRAIR-2039
Dussupt, V., Jensen, J. L., Thomas, P. V., Mendez-Rivera, L., Lal, K. G., McCrea, M. Zemil, Swafford, I., Hernandez, J., Sankhala, R. S., Rao, M., Arora, J., Hajduczki, A., Jian, N., Rees, P. A., De Leon, I. Showell-, Smith, G., Smith, L., Wasson, D., Schmid, A., Teng, I. - T., Zhou, T., Kwong, P. D., Currier, J. R., Reiley, W. W., Paquin-Proulx, D., Polonis, V. R., Collins, N. D., Michael, N. L., M Joyce, G., and Krebs, S. J. (2025) First-generation N-terminal domain supersite public antibodies retain activity against Omicron-derived lineages and protect mice against Omicron BA.5 challenge. mBio. 16, e0103625
9MEY, Crystal structure of RIT1(GDP) bound to LZTR1(Kelch domain)
Dharmaiah, S., Bonsor, D. A., Mo, S. P., Fernandez-Cabrera, A., Chan, A. H., Messing, S., Drew, M., Vega, M., Nissley, D. V., Esposito, D., Castel, P., and Simanshu, D. K. (2025) Structural basis for LZTR1 recognition of RAS GTPases for degradation. Science. 389, 1112-1117
9CML, Crystal structure of p110alpha-RAS binding domain (RBD) in complex with molecular glue D223
Terayama, K., Furuzono, S., Fer, N., Yan, W., Young, L. C., Czyzyk, D. J., de Salazar, R. Goldstein, Sasaki, M., Uozumi, A., Konishi, M., Kanda, S., Sogawa, Y., Yamaguchi, M., Tsuji, T., Kuroyanagi, J., Hayashi, M., Ogura, Y., Simanshu, D. K., Kubota, K., Tanaka, J., and McCormick, F. (2025) Molecular glues that facilitate RAS binding to PI3Kα promote glucose uptake without insulin.. Science. 389, 402-408
Structure of Azospirillum bacterial CARD crystal form 1
Wein, T., Millman, A., Lange, K., Yirmiya, E., Hadary, R., Garb, J., Melamed, S., Amitai, G., Dym, O., Steinruecke, F., Hill, A. B., Kranzusch, P. J., and Sorek, R. (2025) CARD domains mediate anti-phage defence in bacterial gasdermin systems. Nature. 10.1038/s41586-024-08498-3
Crystal structure of the RRAS2-p110alpha complex
Czyzyk, D., Yan, W., Messing, S., Gillette, W., Tsuji, T., Yamaguchi, M., Furuzono, S., Turner, D. M., Esposito, D., Nissley, D. V., McCormick, F., and Simanshu, D. K. (2025) Structural insights into isoform-specific RAS-PI3Kα interactions and the role of RAS in PI3Kα activation.. Nat Commun. 16, 525
Crystal structure of HLA-A*03:01 in complex with a mutant PIK3CA peptide analogue (Trp-6 Bta)
Ma, J., Ayres, C. M., Brambley, C. A., Chandran, S. S., Rosales, T. J., Perera, W. W. J. Gihan, Eldaly, B., Murray, W. T., Corcelli, S. A., Kovrigin, E. L., Klebanoff, C. A., and Baker, B. M. (2025) Dynamic allostery in the peptide/MHC complex enables TCR neoantigen selectivity. Nat Commun. 16, 849
Crystal structure of human hemoglobin in complex with the HbpA receptor from Corynebacterium diphtheriae
Mahoney, B. J., Lyman, L. R., Ford, J., Soule, J., Cheung, N. A., Goring, A. K., Ellis-Guardiola, K., Collazo, M. J., Cascio, D., Ton-That, H., Schmitt, M. P., and Clubb, R. T. (2025) Molecular basis of hemoglobin binding and heme removal in Corynebacterium diphtheriae. Proc Natl Acad Sci U S A. 122, e2411833122
8T0U, Crystal structure of dimethylsulfone monooxygenase SfnG from Pseudomonas fluorescens
Gonzalez, R., Soule, J., Phan, N., Wicht, D. K., and Dowling, D. P. (2024) Structural, biophysical, and biochemical insights into C-S bond cleavage by dimethylsulfone monooxygenase. Proc Natl Acad Sci U S A. 121, e2401858121
Human Argonaute3 bound to cityRNA and target RNA
Zhang, H., Sim, G. Y., Kehling, A. C., Adhav, V. Annasaheb, Savidge, A., Pastore, B., Tang, W., and Nakanishi, K. (2024) Target cleavage and gene silencing by Argonautes with cityRNAs. Cell Rep. 43, 114806
8UTK, IL-23R minibinder - 23R-B04dslf02IB
Berger, S., Seeger, F., Yu, T. - Y., Aydin, M., Yang, H., Rosenblum, D., Guenin-Macé, L., Glassman, C., Arguinchona, L., Sniezek, C., Blackstone, A., Carter, L., Ravichandran, R., Ahlrichs, M., Murphy, M., Pultz, I. Swanson, Kang, A., Bera, A. K., Stewart, L., K Garcia, C., Naik, S., Spangler, J. B., Beigel, F., Siebeck, M., Gropp, R., and Baker, D. (2024) Preclinical proof of principle for orally delivered Th17 antagonist miniproteins. Cell. 187, 4305-4317.e18
8VEI, De novo designed colic acid binder CHD_r1
An, L., Said, M., Tran, L., Majumder, S., Goreshnik, I., Lee, G. Rie, Juergens, D., Dauparas, J., Anishchenko, I., Coventry, B., Bera, A. K., Kang, A., Levine, P. M., Alvarez, V., Pillai, A., Norn, C., Feldman, D., Zorine, D., Hicks, D. R., Li, X., Sanchez, M. Garcia, Vafeados, D. K., Salveson, P. J., Vorobieva, A. A., and Baker, D. (2024) Binding and sensing diverse small molecules using shape-complementary pseudocycles. Science. 385, 276-282
8TZ0, Structure of a bacterial E1-E2-Ubl complex (form 1)
Chambers, L. R., Ye, Q., Cai, J., Gong, M., Ledvina, H. E., Zhou, H., Whiteley, A. T., Suhandynata, R. T., and Corbett, K. D. (2024) A eukaryotic-like ubiquitination system in bacterial antiviral defence. Nature. 631, 843-849
8UTA, yjdF riboswitch from R. gauvreauii in complex with proflavine bound to Fab BL3-6 S97N
Krochmal, D., Roman, C., Lewicka, A., Shao, Y., and Piccirilli, J. A. (2024) Structural basis for promiscuity in ligand recognition by yjdF riboswitch. Cell Discov. 10, 37
8S8K, Structure of dimeric FAM111A SPD S541A Mutant
Palani, S., Machida, Y., Alvey, J. R., Mishra, V., Welter, A. L., Cui, G., Bragantini, B., Botuyan, M. Victoria, Cong, A. T. Q., Mer, G., Schellenberg, M. J., and Machida, Y. J. (2024) Dimerization-dependent serine protease activity of FAM111A prevents replication fork stalling at topoisomerase 1 cleavage complexes. Nat Commun. 15, 2064
Structure of PYCR1 complexed with 3-(6-Oxa-9-azaspiro(4.5)decane-9-carbonyl)benzoic acid
Meeks, K. R., Ji, J., Protopopov, M. V., Tarkhanova, O. O., Moroz, Y. S., and Tanner, J. J. (2024) Novel Fragment Inhibitors of PYCR1 from Docking-Guided X-ray Crystallography. J Chem Inf Model. 64, 1704-1718
Crystal structure of the SARS-CoV-2 receptor binding domain in complex with neutralizing antibody WRAIR-5021
Sankhala, R. S., Lal, K. G., Jensen, J. L., Dussupt, V., Mendez-Rivera, L., Bai, H., Wieczorek, L., Mayer, S. V., Zemil, M., Wagner, D. A., Townsley, S. M., Hajduczki, A., Chang, W. C., Chen, W. - H., Donofrio, G. C., Jian, N., King, H. A. D., Lorang, C. G., Martinez, E. J., Rees, P. A., Peterson, C. E., Schmidt, F., Hart, T. J., Duso, D. K., Kummer, L. W., Casey, S. P., Williams, J. K., Kannan, S., Slike, B. M., Smith, L., Swafford, I., Thomas, P. V., Tran, U., Currier, J. R., Bolton, D. L., Davidson, E., Doranz, B. J., Hatziioannou, T., Bieniasz, P. D., Paquin-Proulx, D., Reiley, W. W., Rolland, M., Sullivan, N. J., Vasan, S., Collins, N. D., Modjarrad, K., Gromowski, G. D., Polonis, V. R., Michael, N. L., Krebs, S. J., and M Joyce, G. (2024) Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques. Nat Commun. 15, 200
8GJG, De novo design of high-affinity protein binders to bioactive helical peptides
Torres, S. Vázquez, J Y Leung, P., Venkatesh, P., Lutz, I. D., Hink, F., Huynh, H. - H., Becker, J., Yeh, A. Hsien- Wei, Juergens, D., Bennett, N. R., Hoofnagle, A. N., Huang, E., MacCoss, M. J., Expòsit, M., Lee, G. Rie, Bera, A. K., Kang, A., De La Cruz, J., Levine, P. M., Li, X., Lamb, M., Gerben, S. R., Murray, A., Heine, P., Korkmaz, E. Nihal, Nivala, J., Stewart, L., Watson, J. L., Rogers, J. M., and Baker, D. (2023) De novo design of high-affinity binders of bioactive helical peptides. Nature. 10.1038/s41586-023-06953-1
Structure of the S1 variant of Fab F1
Bruce, H. A., Singer, A. U., Filippova, E. V., Blazer, L. L., Adams, J. J., Enderle, L., Ben-David, M., Radley, E. H., Mao, D. Y. L., Pau, V., Orlicky, S., Sicheri, F., Kourinov, I., Atwell, S., Kossiakoff, A. A., and Sidhu, S. S. (2023) Engineered Antigen-Binding Fragments for Enhanced Crystallization of Antibody:Antigen Complexes. Protein Sci. 10.1002/pro.4824
GSQASS segment from the Nucleoprotein of SARS-CoV-2, residues 179-184
Tayeb-Fligelman, E., Bowler, J. T., Tai, C. E., Sawaya, M. R., Jiang, Y. Xiao, Garcia, G., Griner, S. L., Cheng, X., Salwinski, L., Lutter, L., Seidler, P. M., Lu, J., Rosenberg, G. M., Hou, K., Abskharon, R., Pan, H., Zee, C. - T., Boyer, D. R., Li, Y., Anderson, D. H., Murray, K. A., Falcon, G., Cascio, D., Saelices, L., Damoiseaux, R., Arumugaswami, V., Guo, F., and Eisenberg, D. S. (2023) Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils. Nat Commun. 14, 2379
Crystal structure of SARS-CoV-2 (Covid-19) Nsp3 macrodomain in complex with TFMU-ADPr
Anmangandla, A., Jana, S., Peng, K., Wallace, S. D., Bagde, S. R., Drown, B. S., Xu, J., Hergenrother, P. J., J Fromme, C., and Lin, H. (2023) A Fluorescence Polarization Assay for Macrodomains Facilitates the Identification of Potent Inhibitors of the SARS-CoV-2 Macrodomain. ACS Chem Biol. 18, 1200-1207
Crystal structure of coxsackievirus B3 cloverleaf RNA replication element
Das, N. K., Hollmann, N. M., Vogt, J., Sevdalis, S. E., Banna, H. A., Ojha, M., and Koirala, D. (2023) Crystal structure of a highly conserved enteroviral 5' cloverleaf RNA replication element. Nat Commun. 14, 1955
7S83
Chen, W. - H., Hajduczki, A., Martinez, E. J., Bai, H., Matz, H., Hill, T. M., Lewitus, E., Chang, W. C., Dawit, L., Peterson, C. E., Rees, P. A., Ajayi, A. B., Golub, E. S., Swafford, I., Dussupt, V., David, S., Mayer, S. V., Soman, S., Kuklis, C., Corbitt, C., King, J., Choe, M., Sankhala, R. S., Thomas, P. V., Zemil, M., Wieczorek, L., Hart, T., Duso, D., Kummer, L., Yan, L., Sterling, S. L., Laing, E. D., Broder, C. C., Williams, J. K., Davidson, E., Doranz, B. J., Krebs, S. J., Polonis, V. R., Paquin-Proulx, D., Rolland, M., Reiley, W. W., Gromowski, G. D., Modjarrad, K., Dooley, H., and M Joyce, G. (2023) Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity. Nat Commun. 14, 580
I-2 Y35N H35N (unbound) Fab from CH65-CH67 lineage
Phillips, A. M., Maurer, D. P., Brooks, C., Dupic, T., Schmidt, A. G., and Desai, M. M. (2023) Hierarchical sequence-affinity landscapes shape the evolution of breadth in an anti-influenza receptor binding site antibody. Elife. 10.7554/eLife.83628
Crystal structure of human METTL1 and WDR4 complex
Li, J., Wang, L., Hahn, Q., Nowak, R. P., Viennet, T., Orellana, E. A., Burman, S. S. Roy, Yue, H., Hunkeler, M., Fontana, P., Wu, H., Arthanari, H., Fischer, E. S., and Gregory, R. I. (2023) Structural basis of regulated mG tRNA modification by METTL1-WDR4. Nature. 613, 391-397
Dalton, K. M., Greisman, J. B., and Hekstra, D. R. (2022) A unifying Bayesian framework for merging X-ray diffraction data. Nat Commun. 13, 7764
Crystal structure of the Thermus thermophilus 70S ribosome in complex with mRNA, aminoacylated A-site Phe-NH-tRNAphe, peptidyl P-site fMSEAC-NH-tRNAmet, and deacylated E-site tRNAphe at 2.40A resolution
Syroegin, E. A., Aleksandrova, E. V., and Polikanov, Y. S. (2022) Insights into the ribosome function from the structures of non-arrested ribosome-nascent chain complexes. Nat Chem. 10.1038/s41557-022-01073-1
Hallucinated C2 protein assembly HALC2_068
Wicky, B. I. M., Milles, L. F., Courbet, A., Ragotte, R. J., Dauparas, J., Kinfu, E., Tipps, S., Kibler, R. D., Baek, M., DiMaio, F., Li, X., Carter, L., Kang, A., Nguyen, H., Bera, A. K., and Baker, D. (2022) Hallucinating symmetric protein assemblies. Science. 378, 56-61
Structure of human TREX1-DNA complex
Zhou, W., Richmond-Buccola, D., Wang, Q., and Kranzusch, P. J. (2022) Structural basis of human TREX1 DNA degradation and autoimmune disease. Nat Commun. 13, 4277
Crystal structure of human TMPRSS2 in complex with Nafamostat
Fraser, B. J., Beldar, S., Seitova, A., Hutchinson, A., Mannar, D., Li, Y., Kwon, D., Tan, R., Wilson, R. P., Leopold, K., Subramaniam, S., Halabelian, L., Arrowsmith, C. H., and Bénard, F. (2022) Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation. Nat Chem Biol. 10.1038/s41589-022-01059-7
Crystal structure of NPR1
Kumar, S., Zavaliev, R., Wu, Q., Zhou, Y., Cheng, J., Dillard, L., Powers, J., Withers, J., Zhao, J., Guan, Z., Borgnia, M. J., Bartesaghi, A., Dong, X., and Zhou, P. (2022) Structural basis of NPR1 in activating plant immunity. Nature. 605, 561-566
7TTM
Liu, L., Iketani, S., Guo, Y., Casner, R. G., Reddem, E. R., Nair, M. S., Yu, J., Chan, J. F. - W., Wang, M., Cerutti, G., Li, Z., Morano, N. C., Castagna, C. D., Corredor, L., Chu, H., Yuan, S., Poon, V. Kwok- Man, Chan, C. Chun- Sing, Chen, Z., Luo, Y., Cunningham, M., Chavez, A., Yin, M. T., Perlin, D. S., Tsuji, M., Yuen, K. - Y., Kwong, P. D., Sheng, Z., Huang, Y., Shapiro, L., and Ho, D. D. (2022) An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses. Sci Transl Med. 10.1126/scitranslmed.abn6859
Crystal structure of SARS-CoV-2 3CL in complex with inhibitor EB46
Liu, H., Iketani, S., Zask, A., Khanizeman, N., Bednarova, E., Forouhar, F., Fowler, B., Hong, S. Jung, Mohri, H., Nair, M. S., Huang, Y., Tay, N. E. S., Lee, S., Karan, C., Resnick, S. J., Quinn, C., Li, W., Shion, H., Xia, X., Daniels, J. D., Bartolo-Cruz, M., Farina, M., Rajbhandari, P., Jurtschenko, C., Lauber, M. A., McDonald, T., Stokes, M. E., Hurst, B. L., Rovis, T., Chavez, A., Ho, D. D., and Stockwell, B. R. (2022) Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19. Nat Commun. 13, 1891
Structure of SARS-CoV-2 main protease in complex with GC376
Moghadasi, S. Arad, Esler, M. A., Otsuka, Y., Becker, J. T., Moraes, S. N., Anderson, C. B., Chamakuri, S., Belica, C., Wick, C., Harki, D. A., Young, D. W., Scampavia, L., Spicer, T. P., Shi, K., Aihara, H., Brown, W. L., and Harris, R. S. (2022) Gain-of-Signal Assays for Probing Inhibition of SARS-CoV-2 M/3CL in Living Cells. mBio. 10.1128/mbio.00784-22
SARS-CoV-2 Receptor Binding Domain in Complex with Ab17
Hauser, B. M., Sangesland, M., St Denis, K. J., Lam, E. C., Case, J. Brett, Windsor, I. W., Feldman, J., Caradonna, T. M., Kannegieter, T., Diamond, M. S., Balazs, A. B., Lingwood, D., and Schmidt, A. G. (2022) Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting. Cell Rep. 38, 110561

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