Yueyang Zhong

University of Michigan, Ann Arbor, Michigan, United States

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Publications (6)33.55 Total impact

  • Yueyang Zhong · Linjie Han · Brandon T Ruotolo
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    ABSTRACT: The three-dimensional structures adopted by proteins are predicated by their many biological functions. Mass spectrometry has played a rapidly expanding role in protein structure discovery, enabling the generation of models for both proteins and their higher-order assemblies. While important coursed-grained insights have been generated, relatively few examples exist where mass spectrometry has been successfully applied to the characterization of protein tertiary structure. Here, we demonstrate that gas-phase unfolding can be used to determine the number of autonomously folded domains within monomeric proteins. Our ion mobility-mass spectrometry data highlight a strong, positive correlation between the number of protein unfolding transitions observed in the gas phase and the number of known domains within a group of sixteen proteins ranging from 8-78 kDa. This correlation and its potential uses for structural biology is discussed.
    No preview · Article · Aug 2014 · Angewandte Chemie International Edition in English
  • Yueyang Zhong · Jun Feng · Brandon T Ruotolo
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    ABSTRACT: Multiprotein complexes have three-dimensional shapes and dynamic functions that impact almost every aspect of biochemistry. Despite this, our ability to rapidly assess the structures of such macromolecules lags significantly behind high-throughput efforts to identify their function, especially in the context of human disease. Here, we describe results obtained by coupling ion mobility-mass spectrometry with automated robotic sampling of different solvent compositions. This combination of technologies has allowed us to explore an extensive set of solution conditions for a group of eight protein homo-tetramers, representing a broad sample of protein structure and stability. We find that altering solution ionic strength in concert with dimethylsulfoxide content is sufficient to disrupt the protein-protein interfaces of all of the complexes studied here. Ion mobility measurements captured for both intact assemblies and subcomplexes matched expected values from available X-ray structures in all cases save two. For these exceptions, we find that distorted subcomplexes result from extreme disruption conditions, and are accompanied by small shifts in intact tetramers size, thus enabling the removal of distorted subcomplex data in downstream models. Furthermore, we find strong correlations between the relative intensities of disrupted protein tetramers and the relative number and type of interactions present at interfaces as a function of disrupting agent added. In most cases, this correlation appears strong enough to quantify various types of protein interfacial interactions within unknown proteins following appropriate calibration.
    No preview · Article · Oct 2013 · Analytical Chemistry
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    ABSTRACT: Maturation of the nickel-containing urease of Klebsiella aerogenes is facilitated by the UreD, UreF, and UreG accessory proteins along with the UreE metallo-chaperone. A fusion of the maltose binding protein and UreD (MBP-UreD) was co-isolated with UreF and UreG in a soluble complex possessing a (MBP-UreD:UreF:UreG)2 quaternary structure. Within this complex a UreF:UreF interaction was identified by chemical cross-linking of the amino termini of its two UreF protomers, as shown by mass spectrometry of tryptic peptides. A pre-activation complex was formed by the interaction of (MBP-UreD:UreF:UreG)2 and urease. Mass spectrometry of intact protein species revealed a pathway for synthesis of the urease pre-activation complex in which individual hetero-trimer units of the (MBP-UreD:UreF:UreG)2 complex bind to urease. Together, these data provide important new insights into the structures of protein complexes associated with urease activation.
    No preview · Article · Jun 2013 · Journal of the American Society for Mass Spectrometry
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    Yueyang Zhong · Suk-Joon Hyung · Brandon T Ruotolo
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    ABSTRACT: Ion mobility coupled to mass spectrometry has been an important tool in the fields of chemical physics and analytical chemistry for decades, but its potential for interrogating the structure of proteins and multiprotein complexes has only recently begun to be realized. Today, ion mobility-mass spectrometry is often applied to the structural elucidation of protein assemblies that have failed high-throughput crystallization or NMR spectroscopy screens. Here, we highlight the technology, approaches and data that have led to this dramatic shift in use, including emerging trends such as the integration of ion mobility-mass spectrometry data with more classical (e.g., 'bottom-up') proteomics approaches for the rapid structural characterization of protein networks.
    Preview · Article · Feb 2012 · Expert Review of Proteomics
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    ABSTRACT: A modular dendrimer-based drug delivery platform was designed to improve upon existing limitations in single dendrimer systems. Using this modular strategy, a biologically active platform containing receptor mediated targeting and fluorescence imaging modules was synthesized by coupling a folic acid (FA) conjugated dendrimer with a fluorescein isothiocyanate (FITC) conjugated dendrimer. The two different dendrimer modules were coupled via the 1,3-dipolar cycloaddition reaction ("click" chemistry) between an alkyne moiety on the surface of the first dendrimer and an azide moiety on the second dendrimer. Two simplified model systems were also synthesized to develop appropriate "click" reaction conditions and aid in spectroscopic assignments. Conjugates were characterized by (1)H NMR spectroscopy and NOESY. The FA-FITC modular platform was evaluated in vitro with a human epithelial cancer cell line (KB) and found to specifically target the overexpressed folic acid receptor.
    Full-text · Article · Mar 2011 · Bioconjugate Chemistry
  • Yueyang Zhong · Suk-Joon Hyung · Brandon T Ruotolo
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    ABSTRACT: High-accuracy, high-resolution ion mobility measurements enable a vast array of important contemporary applications in biological chemistry. With the recent advent of both new, widely available commercial instrumentation and also new calibration datasets tailored for the aforementioned commercial instrumentation, the possibilities for extending such high performance measurements to a diverse set of applications have never been greater. Here, we assess the performance characteristics of a second-generation traveling-wave ion mobility separator, focusing on those figures of merit that lead to making measurements of collision cross-section having both high precision and high accuracy. Through performing a comprehensive survey of instrument parameters and settings, we find instrument conditions for optimized drift time resolution, cross-section resolution, and cross-section accuracy for a range of peptide, protein and multi-protein complex ions. Moreover, the conditions for high accuracy IM results are significantly different from those optimized for separation resolution, indicating that a balance between these two metrics must be attained for traveling wave IM separations of biomolecules. We also assess the effect of ion heating during IM separation on instrument performance.
    No preview · Article · Mar 2011 · The Analyst