Ian A Wilson
Affiliation: The Scripps Research Institute
- Sarkar A, Bale S, Behrens A, Kumar S, Sharma S, de Val N, et al. Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer. Nat Commun. 2018;9:1956 pubmed publisher..Thus, cleavage-independent NFL Env trimers exhibit quaternary protein and carbohydrate structures similar to the native viral spike that further validate their potential as vaccine immunogen candidates. ..
- Xu Q, Mengin Lecreulx D, Patin D, Grant J, Chiu H, Jaroszewski L, et al. Structure-guided functional characterization of DUF1460 reveals a highly specific NlpC/P60 amidase family. Structure. 2014;22:1799-809 pubmed publisher..Further crystal structures of AmiA in complexes with GlcNAc-1,6-anhydro-MurNAc and GlcNAc have enabled us to elucidate substrate recognition and specificity. DUF1460 is highly conserved in structure and defines another amidase family. ..
- Lee P, Zhu X, Yu W, Wilson I. Design and Structure of an Engineered Disulfide-Stabilized Influenza Virus Hemagglutinin Trimer. J Virol. 2015;89:7417-20 pubmed publisher..This platform has been applied to H1 and H3 HAs and provides prospects for design of intact, stabilized influenza virus HA immunogens. ..
- Kong L, Kadam R, Giang E, Ruwona T, Nieusma T, Culhane J, et al. Structure of Hepatitis C Virus Envelope Glycoprotein E1 Antigenic Site 314-324 in Complex with Antibody IGH526. J Mol Biol. 2015;427:2617-28 pubmed publisher..Molecular dynamics simulations indicate that the free peptide is flexible in solution, suggesting that it requires stabilization for use as a candidate vaccine immunogen. ..
- Zhu X, Viswanathan K, Raman R, Yu W, Sasisekharan R, Wilson I. Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants. Cell Rep. 2015;13:1683-91 pubmed publisher..These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses. ..
- Wu N, Thompson A, Xie J, Lin C, Nycholat C, Zhu X, et al. A complex epistatic network limits the mutational reversibility in the influenza hemagglutinin receptor-binding site. Nat Commun. 2018;9:1264 pubmed publisher..Further studies are necessary to elucidate whether such entrenchment limits future options for immune escape or adversely affect long-term viral fitness. ..
- Ward A, Wilson I. Insights into the trimeric HIV-1 envelope glycoprotein structure. Trends Biochem Sci. 2015;40:101-7 pubmed publisher..We describe our current knowledge of the Env trimer structure in the context of exciting recent developments in the identification and characterization of HIV broadly neutralizing antibodies. ..
- Gunn R, Herrin B, Acharya S, Cooper M, Wilson I. VLR Recognition of TLR5 Expands the Molecular Characterization of Protein Antigen Binding by Non-Ig-based Antibodies. J Mol Biol. 2018;430:1350-1367 pubmed publisher..Our work here demonstrates that the lamprey adaptive immune system can be used to generate high-affinity VLR clones that recognize different epitopes and differentially impact natural ligand binding to a protein antigen. ..
- Irimia A, Sarkar A, Stanfield R, Wilson I. Crystallographic Identification of Lipid as an Integral Component of the Epitope of HIV Broadly Neutralizing Antibody 4E10. Immunity. 2016;44:21-31 pubmed publisher..Identification of the lipid binding sites on 4E10 may aid design of immunogens for vaccines that include a lipid component in addition to the MPER on gp41 for generation of broadly neutralizing antibodies. ..
- McLuskey K, Grewal J, Das D, Godzik A, Lesley S, Deacon A, et al. Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome. J Biol Chem. 2016;291:9482-91 pubmed publisher..Collectively, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms. ..
- Wu N, Wilson I. Structural insights into the design of novel anti-influenza therapies. Nat Struct Mol Biol. 2018;25:115-121 pubmed publisher..Here we review milestones in HA structural biology and how the recent insights from bnAbs are paving the way to design novel vaccines and therapeutics. ..
- Garces F, Lee J, de Val N, de la Peña A, Kong L, Puchades C, et al. Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans. Immunity. 2015;43:1053-63 pubmed publisher..664 HIV-1 trimer with a PGT121 family member at 3.0 Ã… that, in concert with these antibody intermediate structures, provides insights to advance design of HIV vaccine candidates. ..
- Guenaga J, Garces F, de Val N, Stanfield R, Dubrovskaya V, Higgins B, et al. Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural Determination of a Stabilized Subtype C HIV Envelope Glycoprotein. Immunity. 2017;46:792-803.e3 pubmed publisher..Env-structure-guided design strategies resulted in multiple homogeneous cross-clade immunogens with the potential to advance HIV vaccine development. ..
- Wright Z, Wu N, Kadam R, Wilson I, Wolan D. Structure-based optimization and synthesis of antiviral drug Arbidol analogues with significantly improved affinity to influenza hemagglutinin. Bioorg Med Chem Lett. 2017;27:3744-3748 pubmed publisher..Our analogues represent novel leads to yield more potent compounds against hemagglutinin that block viral entry. ..
- Medina Ramirez M, Garces F, Escolano A, Skog P, de Taeye S, Del Moral Sanchez I, et al. Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo. J Exp Med. 2017;214:2573-2590 pubmed publisher..2-Å resolution in complex with neutralizing antibodies 35O22 and 9H+109L reveals a native-like conformation and the successful incorporation of design features associated with binding of multiple gl-bNAb precursors. ..
- Lang S, Xie J, Zhu X, Wu N, Lerner R, Wilson I. Antibody 27F3 Broadly Targets Influenza A Group 1 and 2 Hemagglutinins through a Further Variation in VH1-69 Antibody Orientation on the HA Stem. Cell Rep. 2017;20:2935-2943 pubmed publisher..These results have important implications for understanding how to elicit broad antibody responses against influenza virus. ..
- Oyen D, Torres J, Wille Reece U, Ockenhouse C, Emerling D, Glanville J, et al. Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein. Proc Natl Acad Sci U S A. 2017;114:E10438-E10445 pubmed publisher..Both complexes display a compact rsCSP with multiple Fabs bound, with the rsCSP-Fab311 complex forming a highly organized helical structure. Together, these structural insights may aid in the design of a next-generation malaria vaccine. ..
- Pantophlet R, Trattnig N, Murrell S, Lu N, Chau D, Rempel C, et al. Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity. Nat Commun. 2017;8:1601 pubmed publisher..These results provide evidence for utilizing antigenic mimicry to elicit oligomannose-specific bnAbs to HIV-1. ..
- Wu N, Wilson I. A Perspective on the Structural and Functional Constraints for Immune Evasion: Insights from Influenza Virus. J Mol Biol. 2017;429:2694-2709 pubmed publisher..This rapidly increasing knowledge of the evolutionary biology, immunology, structural biology, and virology of influenza virus is invaluable for development and design of more universal influenza vaccines and novel therapeutics. ..
- Tzarum N, de Vries R, Peng W, Thompson A, Bouwman K, McBride R, et al. The 150-Loop Restricts the Host Specificity of Human H10N8 Influenza Virus. Cell Rep. 2017;19:235-245 pubmed publisher..Crystal structures of H10 HA mutants with human and avian receptor analogs, receptor-binding studies, and tissue staining experiments illustrate the important role of the 150-loop in H10 receptor specificity. ..
- Xu Q, Shoji M, Shibata S, Naito M, Sato K, Elsliger M, et al. A Distinct Type of Pilus from the Human Microbiome. Cell. 2016;165:690-703 pubmed publisher..The Bacteroidia pilus, therefore, has a biogenesis mechanism that is distinct from other known pili and likely represents a different type of bacterial pilus. ..
- Blattner C, Lee J, Sliepen K, Derking R, Falkowska E, de la Peña A, et al. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers. Immunity. 2014;40:669-80 pubmed publisher..Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer. ..
- Xu Q, Chiu H, Farr C, Jaroszewski L, Knuth M, Miller M, et al. Structures of a bifunctional cell wall hydrolase CwlT containing a novel bacterial lysozyme and an NlpC/P60 DL-endopeptidase. J Mol Biol. 2014;426:169-84 pubmed publisher..Access to the active site is likely regulated by isomerism of a side chain atop the catalytic cysteine, allowing substrate entry or product release (open state), or catalysis (closed state). ..