Defining proteoform-specific interactions for drug targeting in a native cell signalling environment.

Understanding the dynamics of membrane protein-ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer.

Removal of Subretinal Gas After Pneumatic Retinopexy Under Air Using External Manipulation.

Purpose: To illustrate a technique for the removal of subretinal gas via pars plana vitrectomy (PPV) with air-fluid exchange and simultaneous manipulation with scleral depression.

Methods: PPV to remove subretinal gas causing persistent macula-off retinal detachment was performed in one eye, and the results were evaluated in this case report. Ports were carefully placed to avoid puncturing the retina, which was significantly displaced anteriorly past the ora serrata due to the buoyancy of the subretinal gas with the patient in a supine position.

Leveraging Ion-Ion and Ion-Photon Activation to Improve the Sequencing of Proteins Carrying Multiple Disulfide Bonds: The Human Serum Albumin Case Study.

Gas-phase sequencing of large intact proteins (>30 kDa) via tandem mass spectrometry is an inherently challenging process that is further complicated by the extensive overlap of multiply charged product ion peaks, often characterized by a low signal-to-noise ratio. Disulfide bonds exacerbate this issue because of the need to cleave both the S-S and backbone bonds to liberate sequence informative fragments. Although electron-based ion activation techniques such as electron transfer dissociation (ETD) have been proven to rupture disulfide bonds in whole protein ions, they still struggle to produce extensive sequencing when multiple, concatenated S-S bonds are present on the same large polypeptide chain.