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Author Arthur Laganowsky

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Evidence for Many Unique Solution Structures for Chymotrypsin Inhibitor 2: A Thermodynamic Perspective Derived from vT-ESI-IMS-MS Measurements.

Shannon A Raab, Tarick J El-Baba, Daniel W Woodall, Wen Liu, Yang Liu, Zane Baird, David A Hales, Arthur Laganowsky, David H Russell, David E Clemmer,

Chymotrypsin inhibitor 2 (CI-2) is a classic model for two-state cooperative protein folding and is one of the most extensively studied systems. Alan Fersht, a pioneer in the field of structural biology, has studied the wild-type (wt) and over 100 mutant forms of CI-2 with traditional analytical and biochemical techniques. ... Read more >>

J Am Chem Soc (Journal of the American Chemical Society)
[2020, 142(41):17372-17383]

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Selective regulation of human TRAAK channels by biologically active phospholipids.

Samantha Schrecke, Yun Zhu, Jacob W McCabe, Mariah Bartz, Charles Packianathan, Minglei Zhao, Ming Zhou, David Russell, Arthur Laganowsky,

TRAAK is an ion channel from the two-pore domain potassium (K2P) channel family with roles in maintaining the resting membrane potential and fast action potential conduction. Regulated by a wide range of physical and chemical stimuli, the affinity and selectivity of K2P4.1 toward lipids remains poorly understood. Here we show ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

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Discovery of Potent Charge-Reducing Molecules for Native Ion Mobility Mass Spectrometry Studies.

Jixing Lyu, Yang Liu, Jacob W McCabe, Samantha Schrecke, Lei Fang, David H Russell, Arthur Laganowsky,

There is growing interest in the characterization of protein complexes and their interactions with ligands using native ion mobility mass spectrometry. A particular challenge, especially for membrane proteins, is preserving noncovalent interactions and maintaining native-like structures. Different approaches have been developed to minimize activation of protein complexes by manipulating charge ... Read more >>

Anal. Chem. (Analytical chemistry)
[2020, 92(16):11242-11249]

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Author Correction: Origin of complexity in haemoglobin evolution.

Arvind S Pillai, Shane A Chandler, Yang Liu, Anthony V Signore, Carlos R Cortez-Romero, Justin L P Benesch, Arthur Laganowsky, Jay F Storz, Georg K A Hochberg, Joseph W Thornton,

An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Read more >>

Nature (Nature)
[2020, 583(7816):E26]

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Structure and mechanism of human diacylglycerol O-acyltransferase 1.

Lie Wang, Hongwu Qian, Yin Nian, Yimo Han, Zhenning Ren, Hanzhi Zhang, Liya Hu, B V Venkataram Prasad, Arthur Laganowsky, Nieng Yan, Ming Zhou,

Diacylglycerol O-acyltransferase 1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans1. DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylation of lipids and proteins2,3. How human DGAT1 and other ... Read more >>

Nature (Nature)
[2020, 581(7808):329-332]

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Origin of complexity in haemoglobin evolution.

Arvind S Pillai, Shane A Chandler, Yang Liu, Anthony V Signore, Carlos R Cortez-Romero, Justin L P Benesch, Arthur Laganowsky, Jay F Storz, Georg K A Hochberg, Joseph W Thornton,

Most proteins associate into multimeric complexes with specific architectures1,2, which often have functional properties such as cooperative ligand binding or allosteric regulation3. No detailed knowledge is available about how any multimer and its functions arose during evolution. Here we use ancestral protein reconstruction and biophysical assays to elucidate the origins ... Read more >>

Nature (Nature)
[2020, 581(7809):480-485]

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Insight into the Selectivity of Kir3.2 toward Phosphatidylinositides.

Pei Qiao, Yang Liu, Tianqi Zhang, Amanda Benavides, Arthur Laganowsky,

Activation of G-protein-gated inwardly rectifying potassium channels (Kir3.x) requires the direct binding of phosphorylated phosphatidylinositides (PIPs). Previous studies have established that PIP isoforms activate Kir channels to varying degrees and the binding affinity between PIPs and Kir3.2 appears to be correlated with the level of activation. However, how individual residues ... Read more >>

Biochemistry (Biochemistry)
[2020, 59(22):2089-2099]

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A Sec14-like Phosphatidylinositol Transfer Protein Paralog Defines a Novel Class of Heme-binding Proteins With An Unusual Heme Coordination Mechanism

Danish Khan, Dongju Lee, Gulcin Gulten, Anup Aggarwal, Joshua Wofford, Inna Krieger, Ashutosh Tripathi, John Patrick, Debra Eckert, Arthur Laganowsky, James Sacchettini, Paul Lindahl, Vytas Bankaitis,

Abstract Yeast Sfh5 is an unusual member of the Sec14-like phosphatidylinositol transfer protein (PITP) family. Whereas PITPs are defined by their abilities to transfer phosphatidylinositol between membranes in vitro, and to stimulate phosphoinositide signaling in vivo, Sfh5 does not exhibit these activities. Rather, Sfh5 is a redox-active penta-coordinate high spin ... Read more >>

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Structure and mechanism of a primate ferroportin

Zhenning Ren, Shuai Gao, Jiemin Shen, Lie Wang, Zhichun Xu, Ye Yu, Preetham Bachina, Hanzhi Zhang, Arthur Laganowsky, Nieng Yan, Ming Zhou, Yaping Pan,

Abstract Ferroportin is the only cellular iron exporter in human and essential for iron homoeostasis. Mutations in ferroportin are associated with hemochromatosis or ferroportin diseases characterized by a paradoxical combination of anemia and abnormal accumulation of iron in cells. Ferroportin is also the target of hepcidin, which is a hormone ... Read more >>

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Enhanced Characterization of Membrane Protein Complexes by Ultraviolet Photodissociation Mass Spectrometry.

Sarah N Sipe, John W Patrick, Arthur Laganowsky, Jennifer S Brodbelt,

Development of chemical chaperones to solubilize membrane protein complexes in aqueous solutions has allowed for gas-phase analysis of their native-like assemblies, including rapid evaluation of stability and interacting partners. Characterization of protein primary sequence, however, has thus far been limited. Ultraviolet photodissociation (UVPD) generates a multitude of sequence ions for ... Read more >>

Anal. Chem. (Analytical chemistry)
[2020, 92(1):899-907]

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Probing Heterogeneous Lipid Interactions with Membrane Proteins Using Mass Spectrometry.

John W Patrick, Arthur Laganowsky,

Native mass spectrometry (Native MS) enables the detection of intact membrane protein complexes in the gas phase. Membrane proteins are encapsulated in nonionic detergent micelles that protect them during transfer into the gas phase and preserves structure and noncovalent interactions. Herein, we describe methods to gently transfer membrane protein complexes ... Read more >>

Methods Mol. Biol. (Methods in molecular biology (Clifton, N.J.))
[2019, 2003:175-190]

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Allostery revealed within lipid binding events to membrane proteins.

John W Patrick, Christopher D Boone, Wen Liu, Gloria M Conover, Yang Liu, Xiao Cong, Arthur Laganowsky,

Membrane proteins interact with a myriad of lipid species in the biological membrane, leading to a bewildering number of possible protein-lipid assemblies. Despite this inherent complexity, the identification of specific protein-lipid interactions and the crucial role of lipids in the folding, structure, and function of membrane proteins is emerging from ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2018, 115(12):2976-2981]

Cited: 16 times

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Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1.

Lucie A Bergdoll, Michael T Lerch, John W Patrick, Kendrick Belardo, Christian Altenbach, Paola Bisignano, Arthur Laganowsky, Michael Grabe, Wayne L Hubbell, Jeff Abramson,

The voltage-dependent anion channel (VDAC) is the most abundant protein in the outer mitochondrial membrane and constitutes the primary pathway for the exchange of ions and metabolites between the cytosol and the mitochondria. There is accumulating evidence supporting VDAC's role in mitochondrial metabolic regulation and apoptosis, where VDAC oligomerization has ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2018, 115(2):E172-E179]

Cited: 9 times

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Melting Proteins: Evidence for Multiple Stable Structures upon Thermal Denaturation of Native Ubiquitin from Ion Mobility Spectrometry-Mass Spectrometry Measurements.

Tarick J El-Baba, Daniel W Woodall, Shannon A Raab, Daniel R Fuller, Arthur Laganowsky, David H Russell, David E Clemmer,

Ion mobility and mass spectrometry techniques are coupled with a temperature-controlled electrospray ionization source to follow the structural transitions of ubiquitin in aqueous solution (pH = 3) at elevated solution temperatures (T = 26-96 °C). Changes in the charge state distribution are consistent with a two-state, cooperative unfolding transition having ... Read more >>

J Am Chem Soc (Journal of the American Chemical Society)
[2017, 139(18):6306-6309]

Cited: 17 times

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Determining Membrane Protein-Lipid Binding Thermodynamics Using Native Mass Spectrometry.

Xiao Cong, Yang Liu, Wen Liu, Xiaowen Liang, David H Russell, Arthur Laganowsky,

Membrane proteins are embedded in the biological membrane where the chemically diverse lipid environment can modulate their structure and function. However, the thermodynamics governing the molecular recognition and interaction of lipids with membrane proteins is poorly understood. Here, we report a method using native mass spectrometry (MS), to determine thermodynamics ... Read more >>

J. Am. Chem. Soc. (Journal of the American Chemical Society)
[2016, 138(13):4346-4349]

Cited: 27 times

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The role of the detergent micelle in preserving the structure of membrane proteins in the gas phase.

Eamonn Reading, Idlir Liko, Timothy M Allison, Justin L P Benesch, Arthur Laganowsky, Carol V Robinson,

Despite the growing importance of the mass spectrometry of membrane proteins, it is not known how their transfer from solution into vacuum affects their stability and structure. To address this we have carried out a systematic investigation of ten membrane proteins solubilized in different detergents and used mass spectrometry to ... Read more >>

Angew. Chem. Int. Ed. Engl. (Angewandte Chemie (International ed. in English))
[2015, 54(15):4577-4581]

Cited: 35 times

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Dimerization and heme binding are conserved in amphibian and starfish homologues of the microRNA processing protein DGCR8.

Rachel Senturia, Arthur Laganowsky, Ian Barr, Ian Barr, Brooke D Scheidemantle, Feng Guo,

Human DiGeorge Critical Region 8 (DGCR8) is an essential microRNA (miRNA) processing factor that is activated via direct interaction with Fe(III) heme. In order for DGCR8 to bind heme, it must dimerize using a dimerization domain embedded within its heme-binding domain (HBD). We previously reported a crystal structure of the ... Read more >>

PLoS ONE (PloS one)
[2012, 7(7):e39688]

Cited: 10 times

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An approach to crystallizing proteins by metal-mediated synthetic symmetrization.

Arthur Laganowsky, Minglei Zhao, Angela B Soriaga, Michael R Sawaya, Duilio Cascio, Todd O Yeates,

Combining the concepts of synthetic symmetrization with the approach of engineering metal-binding sites, we have developed a new crystallization methodology termed metal-mediated synthetic symmetrization. In this method, pairs of histidine or cysteine mutations are introduced on the surface of target proteins, generating crystal lattice contacts or oligomeric assemblies upon coordination ... Read more >>

Protein Sci. (Protein science : a publication of the Protein Society)
[2011, 20(11):1876-1890]

Cited: 27 times

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Molecular basis for amyloid-beta polymorphism.

Jacques-Philippe Colletier, Arthur Laganowsky, Meytal Landau, Minglei Zhao, Angela B Soriaga, Lukasz Goldschmidt, David Flot, Duilio Cascio, Michael R Sawaya, David Eisenberg,

Amyloid-beta (Aβ) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. Aβ molecules form β-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of Aβ has frustrated its ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2011, 108(41):16938-16943]

Cited: 140 times

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Towards a pharmacophore for amyloid.

Meytal Landau, Michael R Sawaya, Kym F Faull, Arthur Laganowsky, Lin Jiang, Stuart A Sievers, Jie Liu, Jorge R Barrio, David Eisenberg,

Diagnosing and treating Alzheimer's and other diseases associated with amyloid fibers remains a great challenge despite intensive research. To aid in this effort, we present atomic structures of fiber-forming segments of proteins involved in Alzheimer's disease in complex with small molecule binders, determined by X-ray microcrystallography. The fiber-like complexes consist ... Read more >>

PLoS Biol. (PLoS biology)
[2011, 9(6):e1001080]

Cited: 75 times

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Hydroponics on a chip: analysis of the Fe deficient Arabidopsis thylakoid membrane proteome.

Arthur Laganowsky, Stephen M Gómez, Julian P Whitelegge, John N Nishio,

The model plant Arabidopsis thaliana was used to evaluate the thylakoid membrane proteome under Fe-deficient conditions. Plants were cultivated using a novel hydroponic system, called "hydroponics on a chip", which yields highly reproducible plant tissue samples for physiological analyses, and can be easily used for in vivo stable isotope labeling. ... Read more >>

J Proteomics (Journal of proteomics)
[2009, 72(3):397-415]

Cited: 27 times

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