Article
Biochemical Research Methods
Richard Y-C Huang, Yun Wang, Amy D. Jhatakia, Andy X. Deng, Christine Bee, Shrikant Deshpande, Vangipuram S. Rangan, Natalie Bezman, Olafur Gudmundsson, Guodong Chen
Summary: NKG2A, an immune checkpoint inhibitor, forms a heterodimer with CD94 and recognizes HLA-E antigen. Mass spectrometry techniques can provide insights into the structure of NKG2A/CD94 heterodimer and the mechanisms of antibody interactions with it.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Biochemical Research Methods
Zhi Cheng, Charles Mobley, Sandeep K. Misra, Rama S. Gadepalli, Rachel Hammond, Leonid S. Brown, John M. Rimoldi, Joshua S. Sharp
Summary: Research shows that the membrane environment does not affect bulk solvent radical scavenging activity, but when present with proteins, the radical scavengers in the membrane compete for the local concentration of hydroxyl radicals, resulting in reduced oxidation of membrane proteins.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Physics, Atomic, Molecular & Chemical
Ruidong Jiang, Don L. Rempel, Michael L. Gross
Summary: Although protein footprinting is commonly done by ESI-based LC-MS/MS, there is a need for a faster alternative method to expand its scope and facilitate routine analysis. In this study, we explore the feasibility of developing a MALDI-based analysis method for footprinting. The approach was successfully applied to several model proteins and demonstrated the capability to accurately assess protein conformational changes.
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
(2023)
Review
Biochemistry & Molecular Biology
Hsin-Chieh Yang, Weikai Li, Jie Sun, Michael L. Gross
Summary: Understanding the higher-order structure of membrane proteins is crucial for comprehending their function. Recent advances in mass spectrometry have provided opportunities in resolving the dynamics and structures of membrane proteins. This review article discusses the challenges and achievements in using mass spectrometry techniques, including hydrogen deuterium exchange, native mass spectrometry, and footprinting methods.
Article
Chemistry, Physical
Catherine Ghosh, Biman Jana
Summary: Anfinsen's dogma, which states that one sequence corresponds to one unique structure necessary for protein functioning, has been challenged by recent discoveries. Proteins have been found to have multiple functions and be able to switch folding structures. In this study, we examined the folding pathways of the metamorphic protein MAD2 and discovered that it can fold into two alternate states through different intermediates. The protein contacts and communication between the N and C termini play a crucial role in determining the folding pathway. This work also provides insights into the preference of a MAD2 variant to exist in the open state.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemistry & Molecular Biology
Sara S. Ribeiro, David Gnutt, Salome Azoulay-Ginsburg, Zamira Fetahaj, Ella Spurlock, Felix Lindner, Damon Kuz, Yfat Cohen-Erez, Hanna Rapaport, Adrian Israelson, Arie-lev Gruzman, Simon Ebbinghaus
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder characterized by the accumulation of unfolded/misfolded superoxide dismutase 1 (SOD1) in different subcellular locations. Recent studies have shown that combining organelle-targeting therapies with chemical chaperones can reduce the subcellular load of misfolded SOD1 and improve cellular processes. This research investigated the effect of targeted chemical chaperones on the folding stability of SOD1 mutants in specific organelles and discovered a novel chemical chaperone, ER-15, that increased the folding stability of ER-SOD1 mutants, suggesting potential therapeutic applications for ALS treatment.
BIOLOGICAL CHEMISTRY
(2023)
Article
Physics, Atomic, Molecular & Chemical
Ruidong Jiang, Don L. Rempel, Michael L. Gross
Summary: Irreversible protein footprinting is a mass spectrometry-based method for assessing high-order protein structure by modifying solvent-accessible sites of a protein. The commonly used bottom-up LC-MS/MS approach is time-consuming and difficult to accelerate for high-throughput analysis. In this study, the authors used matrix-assisted laser desorption/ionization (MALDI) in-source decay (ISD) to analyze a footprinted small test protein (ubiquitin) via a top-down approach. They optimized the method with model peptides and demonstrated its feasibility for fast footprinting analysis. MALDI ISD provided a comprehensive set of fragment ions and gave results consistent with established methods, serving as a rough measure of protein solvent accessibility.
EUROPEAN JOURNAL OF MASS SPECTROMETRY
(2023)
Article
Biochemical Research Methods
Ben Niu, Hao Zhang, Daryl Giblin, Don L. Rempel, Michael L. Gross
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2015)
Article
Biochemical Research Methods
Ben Niu, Brian C. Mackness, Don. L. Rempel, Hao Zhang, Weidong Cui, C. Robert Matthews, Jill A. Zitzewitz, Michael L. Gross
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2017)
Article
Medicine, Research & Experimental
Mingyan Cao, Niluka De Mel, Anthony Shannon, Meagan Prophet, Chunlei Wang, Weichen Xu, Ben Niu, Jun Kim, Methal Albarghouthi, Dengfeng Liu, Eric Meinke, Shihua Lin, Xiangyang Wang, Jihong Wang
Article
Chemistry, Medicinal
Mingyan Cao, Weichen Xu, Ben Niu, Ivy Kabundi, Haibin Luo, Meagan Prophet, Weimin Chen, Dengfeng Liu, Sergei Saveliev, Marjeta Urh, Jihong Wang
JOURNAL OF PHARMACEUTICAL SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Ben Niu, Todd C. Appleby, Ruth Wang, Mariya Morar, Johannes Voight, Armando G. Villasenor, Sheila Clancy, Sarah Wise, Jean-Philippe Belzile, Giuseppe Papalia, Melanie Wong, Katherine M. Brendza, Latesh Lad, Michael L. Gross
Article
Multidisciplinary Sciences
Ben Niu, Michael Martinelli II, Yang Jiao, Chunlei Wang, Mingyan Cao, Jihong Wang, Eric Meinke
Article
Multidisciplinary Sciences
Que N. Van, Cesar A. Lopez, Marco Tonelli, Troy Taylor, Ben Niu, Christopher B. Stanley, Debsindhu Bhowmik, Timothy H. Tran, Peter H. Frank, Simon Messing, Patrick Alexander, Daniel Scott, Xiaoying Ye, Matt Drew, Oleg Chertov, Mathias Losche, Arvind Ramanathan, Michael L. Gross, Nicolas W. Hengartner, William M. Westler, John L. Markley, Dhirendra K. Simanshu, Dwight Nissley, William K. Gillette, Dominic Esposito, Frank McCormick, S. Gnanakaran, Frank Heinrich, Andrew G. Stephen
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemical Research Methods
Trina Mouchahoir, John E. Schiel, Rich Rogers, Alan Heckert, Benjamin J. Place, Aaron Ammerman, Xiaoxiao Li, Tom Robinson, Brian Schmidt, Chris M. Chumsae, Xinbi Li, Anton Manuilov, Bo Yan, Gregory O. Staples, Da Ren, Alexander J. Veach, Dongdong Wang, Wael Yared, Zoran Sosic, Yan Wang, Li Zang, Anthony M. Leone, Peiran Liu, Richard Ludwig, Li Tao, Wei Wu, Ahmet Cansizoglu, Andrew Hanneman, Greg W. Adams, Irina Perdivara, Hunter Walker, Margo Wilson, Arnd Brandenburg, Nick DeGraan-Weber, Stefano Gotta, Joe Shambaugh, Melissa Alvarez, X. Christopher Yu, Li Cao, Chun Shao, Andrew Mahan, Hirsh Nanda, Kristen Nields, Nancy Nightlinger, Helena Maria Barysz, Michael Jahn, Ben Niu, Jihong Wang, Gabriella Leo, Nunzio Sepe, Yan-Hui Liu, Bhumit A. Patel, Douglas Richardson, Yi Wang, Daniela Tizabi, Oleg Borisov, Yali Lu, Ernest L. Maynard, Albrecht Gruhler, Kim F. Haselmann, Thomas N. Krogh, Carsten P. Sonksen, Simon Letarte, Sean Shen, Kristin Boggio, Keith Johnson, Wenqin Ni, Himakshi Patel, David Ripley, Jason C. Rouse, Ying Zhang, Carly Daniels, Andrew Dawdy, Olga Friese, Thomas W. Powers, Justin B. Sperry, Josh Woods, Eric Carlson, K. Ilker Sen, St John Skilton, Michelle Busch, Anders Lund, Martha Stapels, Xu Guo, Sibylle Heidelberger, Harini Kaluarachchi, Sean McCarthy, John Kim, Jing Zhen, Ying Zhou, Sarah Rogstad, Xiaoshi Wang, Jing Fang, Weibin Chen, Ying Qing Yu, John G. Hoogerheide, Rebecca Scott, Hua Yuan
Summary: The MAM Consortium conducted an interlaboratory study to evaluate NPD performance across the industry, with results showing representative high-resolution MS capabilities. Critical elements of NPD were identified to further refine the methodology and speed up adoption into manufacturer-specific protein therapeutic product life cycles.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Chemistry, Analytical
Chen Qian, Ben Niu, Rod Brian Jimenez, Jihong Wang, Methal Albarghouthi
Summary: The multi-attribute method based on liquid chromatography-tandem mass spectrometry is a powerful tool for monitoring multiple product quality attributes simultaneously, and a need for a universal and high-throughput workflow has been identified to better implement this method. Manual sample preparation for MAM is labor intensive and produces variations, therefore a fully automated peptide mapping procedure has been developed to improve sample handling capacity and outcome reproducibility.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Biochemical Research Methods
Lucas K. Kimerer, Ben Niu, Timothy M. Pabst, Weiguo Zhai, Alan K. Hunter, Giorgio Carta
Summary: The study on elution and adsorptive behavior of a bivalent bispecific antibody and associated fragments on two cation exchange chromatography media revealed that configurational flexibility affects multi-peak elution behavior, while mass transfer limitations lead to broader peaks that obscure the multi-peak elution behavior.
JOURNAL OF CHROMATOGRAPHY A
(2021)
Article
Biotechnology & Applied Microbiology
Siddharth S. Parasnavis, Ben Niu, Matthew Aspelund, Wai K. Chung, Mark Snyder, Steven M. Cramer
Summary: A systematic workflow was developed to investigate selectivity differences and preferred binding patches for bispecific monoclonal antibodies and their parental antibodies on multimodal cation exchange resin systems. Chromatographic screening, surface property mapping, and protein footprinting were utilized to analyze the interactions of intact antibodies and fragments, revealing that interactions with the resins were primarily driven by the Fab fragments. The study provides insights into the chromatographic selectivity of large multidomain molecules and can contribute to improved biomanufacturability and downstream bioprocess development.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Biochemical Research Methods
Ben Niu, Michael Martinelli, Niluka de Mel, Eric Meinke, Weiguo Zhai, Greg Kilby, Wei Xu, Xiaoyu Chen, Chunlei Wang
Summary: Therapeutic monoclonal antibodies (mAbs) are heterogeneous and require a variety of separation methods for study and control. Protein oxidation introduced during fractionation may complicate data interpretation, with higher-energy detectors and lower fraction concentrations exacerbating the issue. Solutions with oxidation scavengers can effectively eliminate oxidation artifacts and improve peak assignment accuracy.
JOURNAL OF CHROMATOGRAPHY A
(2022)