Most ebook files are in PDF format, so you can easily read them using various software such as Foxit Reader or directly on the Google Chrome browser.
Some ebook files are released by publishers in other formats such as .awz, .mobi, .epub, .fb2, etc. You may need to install specific software to read these formats on mobile/PC, such as Calibre.
Please read the tutorial at this link. https://ebooknice.com/page/post?id=faq
We offer FREE conversion to the popular formats you request; however, this may take some time. Therefore, right after payment, please email us, and we will try to provide the service as quickly as possible.
For some exceptional file formats or broken links (if any), please refrain from opening any disputes. Instead, email us first, and we will try to assist within a maximum of 6 hours.
EbookNice Team
Status:
Available4.9
19 reviewsSUMMARYApelin is a key hormone in cardiovascular homeostasis that activates the apelin receptor (APLNR), which isregarded as a promising therapeutic target for cardiovascular disease. However, adverse effects through theb-arrestin pathway limit its pharmacological use. Here, we report cryoelectron microscopy (cryo-EM) structures of APLNR-Gi1 complexes bound to three agonists with divergent signaling profiles. Combined withfunctional assays, we have identified ‘‘twin hotspots’’ in APLNR as key determinants for signaling bias, guiding the rational design of two exclusive G-protein-biased agonists WN353 and WN561. Cryo-EM structures ofWN353- and WN561-stimulated APLNR-G protein complexes further confirm that the designed ligands adoptthe desired poses. Pathophysiological experiments have provided evidence that WN561 demonstrates superior therapeutic effects against cardiac hypertrophy and reduced adverse effects compared with the established APLNR agonists. In summary, our designed APLNR modulator may facilitate the development ofnext-generation cardiovascular medications.
4.4
39 reviews
4.5
6 reviews