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However, such heterodimer specific allosteric ligands offer obvious opportunities, modulating the function of the partner GPCR only in the presence of the orthosteric ligand for that receptor and doing so only in cells and tissues in which the relevant heterodimer is expressed [ 25].
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Although PST is known not to interfere the function of the fusion partner (Kobayashi et al. 2009), we next examined the inhibitory activity of the purified His6-PrS2-Bac7 (1–35) using a cell-free protein synthesis system (New England BioLabs) comparing with the inhibitory ability of intact fusion protein.
At present, the functional consequence of this arrangement for many of these gene-pairs remains unclear, but the possibility that targeted mutation of one gene could affect expression or function of the other partner in the transcription unit should be considered.
Although S100A4 is known to bind to a number of cellular proteins, it remains to be determined how these interactions affect the function of the binding partners, and whether these interactions are relevant to the metastatic phenotype.
Such an effect might then alter the orthosteric binding pocket or function of the GPCR heterodimer partner.
It is hoped that further dissection of the functions of the novel partner proteins, present in complexes either with BRCA1 or BRCA2, will help to define the precise roles of BRCA1 and BRCA2 in DSB repair.
The function of the steady binding partners was less obvious, but their stimulation-independent and non-dynamic association to SLP65 was consistent with the functional properties of a preformed BCR transducer complex that was predicted based on genetic evidence and explained the efficient coupling of BCR-proximal effector molecules (Wienands et al, 1996).
The analysis of functional assignment for individual proteins and all protein pairs showed that the frequency of interaction between proteins depended on the function of each partner and on connectivity.
On loss of an initial gene, interference with the function of its partner gene(s) may result in cell death, a phenomenon known as synthetic lethality.
The biological function encoded by each nORF, if any, remains to be elucidated, and further work is required to characterize the functions of the overlapping partners.
Sanders et al [ 2] showed that 15 (13%) of 114 prepubertal boys developed normal testicular function and the partners of 2 of them became pregnant; the great majority of those who recovered testicular function had been given cyclophosphamide without irradiation.
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