2019
DOI: 10.1002/bip.23329
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Comprehensive structural modeling and preparation of human 5‐HT2A G‐protein coupled receptor in functionally active form

Abstract: The serotonin 2A receptor (5-HT 2A R) is an important member of the G-protein coupled receptor (GPCR) family involved in an array of neuromodulatory functions. Although the high-resolution structures of truncated versions of GPCRs, captured in ligand-bound conformational states, are available, the structures lack several functional regions, which have crucial roles in receptor response. Here, in order to understand the structure and dynamics of the ligand-free form of the receptor, we have performed meticulous… Show more

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Cited by 10 publications
(15 citation statements)
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References 59 publications
(96 reference statements)
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“…Hence, it may be prudent to optimize these factors, especially if it is more economical to expend baculoviral stock and save PBA, or vice versa. Moreover, as noted previously (Mozumder et al, 2020), the extent of glycosylation in cultures grown with PBA can be modulated by varying the post-infection harvest time. Hence the time of harvest may also be optimized to select the desirable amount of glycosylation, by running Western blot analysis of cell lysate from cultures grown over a range of post-infection harvest times (see for suitable buffers for Western blotting).…”
Section: Discussionmentioning
confidence: 58%
“…Hence, it may be prudent to optimize these factors, especially if it is more economical to expend baculoviral stock and save PBA, or vice versa. Moreover, as noted previously (Mozumder et al, 2020), the extent of glycosylation in cultures grown with PBA can be modulated by varying the post-infection harvest time. Hence the time of harvest may also be optimized to select the desirable amount of glycosylation, by running Western blot analysis of cell lysate from cultures grown over a range of post-infection harvest times (see for suitable buffers for Western blotting).…”
Section: Discussionmentioning
confidence: 58%
“…However, intracellular loops, in particular ICL3, play an important role in receptor activation due to their interaction with G proteins and the influence on G protein preferential coupling [32][33][34]. Recently, a full model of human serotonin 5-HT 2A receptor has been reported as an example of this challenging loop modeling [15].…”
Section: Discussionmentioning
confidence: 99%
“…In spite of about 350 GPCR crystal structures including 85 active structures [14] in the Protein Data Bank, the full experimentally solved structures of receptors with long and flexible ICL3 are not yet available. Due to limitations of experimental methods, at present, such structures can be only obtained using molecular modeling approaches as it has been recently done, e.g., for the human serotonin 5-HT 2A receptor [15]. In this work, we aimed to construct complete models of D 2S and D 2L isoforms in complex with dopamine and both G i1 and G i2 proteins and, subsequently, to examine possible G protein coupling preferences of these isoforms and the receptor activation/deactivation hallmarks upon agonist binding and G protein coupling with molecular dynamics (MD) techniques.…”
Section: Introductionmentioning
confidence: 99%
“…It would be worthwhile to mention at this point that the probability of relation between two separate systems was discussed mathematically by Schrodinger [34,35] . If there is a common observable in the two systems (in our case the sin/ion transfer between NAM and the diseased cell and between NAM and medicinal molecules to get the signature of the medicinal molecules) and when such two observable are related coherently to some of their states of the two systems, by some definite common observable (ions/sins transfer in both the MAM and DC systems) one to one correspondence persists as time advances and the observables of the first system (say NAM) change their ions/electrons in the way that the observables in the second system (say in the DC) undergo a certain contacttransformation [36,37] . Definitely the situation is complex executing a new field of research, called Quantum Biology [38,41] (where physics meets biology), which is still in the developing state.…”
Section: Involvement Of Quantum Mechanism With (Nam) and (Lcl)mentioning
confidence: 99%