Use of Isotope-Edited FTIR to Derive a Backbone Structure of a Transmembrane Protein

Manor, Joshua; Arbely, Eyal; Beerlink, André; Akkawi, Mutaz; Arkin, Isaiah T.

doi:10.1021/jz501055d

Cited by 13 publications

(18 citation statements)

References 32 publications

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“…Depending on the CoV, E protein may be glycosylated [148], palmitoylated [149] and ubiquinated [150]. These conclusions have been extensively confirmed [151][152][153], although unfortunately, a high-resolution X-ray or cryoEM structure is not yet available. Deletions in various parts of the E protein throughout its length produces an attenuated virus.…”

Section: The Envelope (E) Protein: Viral Assemblymentioning

confidence: 94%

The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis

Wong

Saier

2021

IJMS

108

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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of Betacoronavirus that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic Betacoronaviruses include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family. We include information on their structures, functions, and participation in pathogenesis. While the shared proteins among the different coronaviruses may vary in structure and function, they all seem to be multifunctional, a common theme interconnecting these viruses. Many transmembrane proteins encoded within the SARS-CoV-2 genome play important roles in the infection cycle while others have functions yet to be understood. We compare the various structural and nonstructural proteins within the Coronaviridae family to elucidate potential overlaps and parallels in function, focusing primarily on the transmembrane proteins and their influences on host membrane arrangements, secretory pathways, cellular growth inhibition, cell death and immune responses during the viral replication cycle. We also offer bioinformatic analyses of potential viroporin activities of the membrane proteins and their sequence similarities to the Envelope (E) protein. In the last major part of the review, we discuss complement, stimulation of inflammation, and immune evasion/suppression that leads to CoV-derived severe disease and mortality. The overall pathogenesis and disease progression of CoVs is put into perspective by indicating several stages in the resulting infection process in which both host and antiviral therapies could be targeted to block the viral cycle. Lastly, we discuss the development of adaptive immunity against various structural proteins, indicating specific vulnerable regions in the proteins. We discuss current CoV vaccine development approaches with purified proteins, attenuated viruses and DNA vaccines.

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Section: The Envelope (E) Protein: Viral Assemblymentioning

confidence: 94%

The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis

Wong

Saier

2021

IJMS

108

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“…In the first class, the labeled C=O group is used as a stand-alone probe of the local structure and environment of proteins (22–26). Recent examples of this include studies of local hydration dynamics (27–29), protein folding thermodynamics and kinetics (30), ligand binding (31–33), peptide-membrane interactions (34, 35), and membrane peptide structure determination (36). In the second class, vibrational coupling between two or more labeled carbonyl groups is used to provide protein structural information at the secondary or tertiary level.…”

Section: Backbone-based Ir Probesmentioning

confidence: 99%

Site-Specific Infrared Probes of Proteins

Pazos²,

Zhang³

et al. 2015

Annu. Rev. Phys. Chem.

164

189

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Infrared spectroscopy has played an instrumental role in studying a wide variety of biological questions. However, in many cases it is impossible or difficult to rely on the intrinsic vibrational modes of biological molecules of interest, such as proteins, to reveal structural and/or environmental information in a site-specific manner. To overcome this limitation, many recent efforts have been dedicated to the development and application of various extrinsic vibrational probes that can be incorporated into biological molecules and used to site-specifically interrogate their structural and/or environmental properties. In this Review, we highlight some recent advancements of this rapidly growing research area.

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“…Isotope-edited IR spectroscopy has been fruitful for uncovering site-specific information of peptides in solution as well as in the membrane (26)(27)(28)(29)(31)(32)(33)(34)(35)(36)(37)(38). For instance, Rothschild and co-workers (35) used isotope labeling to probe the local secondary structure and orientation of the membrane-anchoring region of an ion channel.…”

Section: Introductionmentioning

confidence: 99%

Site-Specific Peptide Probes Detect Buried Water in a Lipid Membrane

Flanagan

Baiz

2019

Biophysical Journal

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Transmembrane peptides contain polar residues in the interior of the membrane, which may alter the electrostatic environment and favor hydration in the otherwise nonpolar environment of the membrane core. Here, we demonstrate a general, nonperturbative strategy to probe hydration of the peptide backbone at specific depths within the bilayer using a combination of site-specific isotope labels, ultrafast two-dimensional infrared spectroscopy, and spectral modeling based on molecular dynamics simulations. Our results show that the amphiphilic pH-low insertion peptide supports a highly heterogeneous environment, with significant backbone hydration of nonpolar residues neighboring charged residues. For example, a leucine residue located as far as 1 nm into the hydrophobic bulk reports hydrogen-bonded populations as high as $20%. These findings indicate that the polar nature of these residues may facilitate the transport of water molecules into the hydrophobic core of the membrane.

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Use of Isotope-Edited FTIR to Derive a Backbone Structure of a Transmembrane Protein

Cited by 13 publications

References 32 publications

The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis

The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis

Site-Specific Infrared Probes of Proteins

Site-Specific Peptide Probes Detect Buried Water in a Lipid Membrane

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