Publications by authors named "T Gopinath"

64 Publications

PHRONESIS: A One-Shot Approach for Sequential Assignment of Protein Resonances by Ultrafast MAS Solid-State NMR Spectroscopy.

Chemphyschem 2022 May 2:e202200127. Epub 2022 May 2.

Department of Biochemistry, Molecular Biology & Biophysics -, University of Minnesota, 321 Church St. SE, Minneapolis, MN 55455, USA.

Solid-state NMR (ssNMR) spectroscopy has emerged as the method of choice to analyze the structural dynamics of fibrillar, membrane-bound, and crystalline proteins that are recalcitrant to other structural techniques. Recently, H detection under fast magic angle spinning and multiple acquisition ssNMR techniques have propelled the structural analysis of complex biomacromolecules. However, data acquisition and resonance-specific assignments remain a bottleneck for this technique. Here, we present a comprehensive multi-acquisition experiment (PHRONESIS) that simultaneously generates up to ten 3D H-detected ssNMR spectra. PHRONESIS utilizes broadband transfer and selective pulses to drive multiple independent polarization pathways. High selectivity excitation and de-excitation of specific resonances were achieved by high-fidelity selective pulses that were designed using a combination of an evolutionary algorithm and artificial intelligence. We demonstrated the power of this approach with microcrystalline U- C, N GB1 protein, reaching 100 % of the resonance assignments using one data set of ten 3D experiments. The strategy outlined in this work opens up new avenues for implementing novel H-detected multi-acquisition ssNMR experiments to speed up and expand the application to larger biomolecular systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cphc.202200127DOI Listing
May 2022

Decoding the influence of the immune system and immunotherapy targets on carcinomas: A hidden prism in oral cancer therapy.

Dis Mon 2022 Mar 17:101353. Epub 2022 Mar 17.

Nitte (Deemed to be University) , AB Shetty Memorial Institute of Dental Sciences (ABSMIDS) , Department of Oral and Maxillofacial Surgery, Mangalore, India.

In recent decades, understanding tumorigenesis and the complex interaction between the host and the immune system has been the pillar for significant advances in anticancer therapy. Conventional anticancer therapy (e.g., cut, burn, and cytotoxic drugs) involves multiple targeting of tumor cells. However, the tumor tissue microenvironment can present a dysregulated, stimulating, or subverted immune response which, in turn, reveals pro-tumor activities favoring tumor expansion and progression. Recently, new potential targets have been identified based on immunomodulatory therapies, which are crafted to re-establish the host anti-tumoral immune response. Clinicians should fully understand the intricate interactions between carcinogens, the tumor milieu, the immune system, and traditional anticancer therapies in order to progress and to overcome the refractory/recurrent challenges and morbidity of the disease. Thus, in this article, we highlight the complex milieu of the oral cancer immune response, pointing out potential therapeutic immunotargets for oral squamous cell carcinomas. The impact of traditional anticancer therapy on the immune system is also outlined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.disamonth.2022.101353DOI Listing
March 2022

Role of Facial Index and Odontometric Parameters in the Establishment of Stature and Gender of Individuals.

J Pharm Bioallied Sci 2021 Nov 10;13(Suppl 2):S1068-S1073. Epub 2021 Nov 10.

Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India.

Background: Dental anthropology is an important aspect of bioarchaeology and forensic anthropology. In forensic anthropological studies, identifying an unknown individual from a mangled and decomposing body is a challenging task. Cranial remains are the only critical clues available for personal identification. Age, sex, and stature are significant parameters in establishing the identity of an unrecognized individual. Stature is the natural height of the individual in an upright position. Stature can be estimated from various parts of the body such as long bones, short bones, and skull. Few studies conducted in specific population have established a correlation for predicting stature from cephalometric and odontometric parameters. Thus, the present study was conducted to determine stature and gender based on cephalometric and odontometric parameters in the population of Tamil Nadu.

Aims: The aim of this study was to investigate the possibility of predicting the stature and gender of an individual based on odontometric measurements, facial height, and bizygomatic width.

Materials And Methods: A total of seventy individuals in the age group of 18-24 years were selected for the study. The facial height, bizygomatic width and length ,mesiodistal and labiolingual diameter of clinical crown of maxillary central,lateral and canine teeth of both the right and left quadrants were measured. The values were analyzed statistically. Through this analysis, regression equations for estimation of stature from odontometric and facial index were derived.

Results: Pearson correlation test was carried out to establish a correlation between the stature and the measured parameters. Regression analysis was carried out to establish stature from the odontometric and facial index of the individual. The regression equations were used to get estimated stature in the same sample of volunteers from which regression equations were obtained. Tabulated results showed a probable correlation between various parameters.

Conclusion: In our study, a positive correlation between cephalometric measurements, gender, crown length of permanent left central incisor, and combined mesiodistal diameter of permanent maxillary anteriors with stature was found. This can be used as a supplementary method for estimating the stature of unknown human bodies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jpbs.jpbs_158_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687007PMC
November 2021

A kink in DWORF helical structure controls the activation of the sarcoplasmic reticulum Ca-ATPase.

Structure 2022 03 6;30(3):360-370.e6. Epub 2021 Dec 6.

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 6-155 Jackson Hall, Minneapolis, MN 55455, USA; Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

SERCA is a P-type ATPase embedded in the sarcoplasmic reticulum and plays a central role in muscle relaxation. SERCA's function is regulated by single-pass membrane proteins called regulins. Unlike other regulins, dwarf open reading frame (DWORF) expressed in cardiac muscle has a unique activating effect. Here, we determine the structure and topology of DWORF in lipid bilayers using a combination of oriented sample solid-state NMR spectroscopy and replica-averaged orientationally restrained molecular dynamics. We found that DWORF's structural topology consists of a dynamic N-terminal domain, an amphipathic juxtamembrane helix that crosses the lipid groups at an angle of 64°, and a transmembrane C-terminal helix with an angle of 32°. A kink induced by Pro15, unique to DWORF, separates the two helical domains. A single Pro15Ala mutant significantly decreases the kink and eliminates DWORF's activating effect on SERCA. Overall, our findings directly link DWORF's structural topology to its activating effect on SERCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.str.2021.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897251PMC
March 2022

Structural basis for sarcolipin's regulation of muscle thermogenesis by the sarcoplasmic reticulum Ca-ATPase.

Sci Adv 2021 Nov 26;7(48):eabi7154. Epub 2021 Nov 26.

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.

The sarcoplasmic reticulum (SR) Ca-ATPase (SERCA) plays a central role in muscle contractility and nonshivering thermogenesis. SERCA is regulated by sarcolipin (SLN), a single-pass membrane protein that uncouples Ca transport from ATP hydrolysis, promoting futile enzymatic cycles and heat generation. The molecular determinants for regulating heat release by the SERCA/SLN complex are unclear. Using thermocalorimetry, chemical cross-linking, and solid-state NMR spectroscopy in oriented phospholipid bicelles, we show that SERCA’s functional uncoupling and heat release rate are dictated by specific SERCA/SLN intramembrane interactions, with the carboxyl-terminal residues anchoring SLN to the SR membrane in an inhibitory topology. Systematic deletion of the carboxyl terminus does not prevent the SERCA/SLN complex formation but reduces uncoupling in a graded manner. These studies emphasize the critical role of lipids in defining the active topology of SLN and modulating the heat release rate by the SERCA/SLN complex, with implications in fat metabolism and basal metabolic rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abi7154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626070PMC
November 2021
-->