PMC:4504005 / 1944-3490
Annnotations
TEST0
{"project":"TEST0","denotations":[{"id":"25982113-176-184-8318979","span":{"begin":386,"end":390},"obj":"[\"15808821\", \"15808821\", \"15808821\"]"},{"id":"25982113-113-121-8318980","span":{"begin":785,"end":789},"obj":"[\"21722971\", \"21722971\", \"21722971\"]"},{"id":"25982113-124-132-8318981","span":{"begin":1079,"end":1083},"obj":"[\"20966082\", \"20966082\", \"20966082\"]"},{"id":"25982113-147-155-8318982","span":{"begin":1102,"end":1106},"obj":"[\"17715056\", \"17715056\", \"17715056\"]"},{"id":"25982113-169-177-8318983","span":{"begin":1124,"end":1128},"obj":"[\"18801728\", \"18801728\", \"18801728\"]"},{"id":"25982113-175-183-8318984","span":{"begin":1130,"end":1134},"obj":"[\"19674967\", \"19674967\", \"19674967\"]"},{"id":"25982113-197-205-8318985","span":{"begin":1152,"end":1156},"obj":"[\"18375760\", \"18375760\", \"18375760\"]"},{"id":"25982113-217-225-8318986","span":{"begin":1172,"end":1176},"obj":"[\"18287102\", \"18287102\", \"18287102\"]"},{"id":"25982113-233-241-8318987","span":{"begin":1196,"end":1200},"obj":"[\"19861722\", \"19861722\", \"19861722\"]"}],"text":"G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that regulate a multitude of biological processes in response to a diverse array of stimuli and they are important drug targets. The class B/Secretin family GPCRs in humans include 15 receptors that are activated by diverse neuropeptides, peptide paracrine factors, and peptide endocrine hormones (Hoare, 2005). These receptors are less well understood than the larger class A/Rhodopsin family, despite their physiological and clinical importance. Class B GPCRs comprise an extracellular domain (ECD) of about 120 amino acids in addition to the 7-transmembrane (7TM) domain in the membrane. The ECD has an N-terminal α-helix and a set of β sheets held together by three disulfide bonds (Archbold et al., 2011). Peptides bind class B GPCRs via a “two-domain” model whereby their C-terminal region binds the ECD and their N-terminal region binds and activates the 7TM domain. Crystal structures are available for class B GPCR ECDs with bound peptides related to PTH, CRF, GIP, and GLP-1 (Pal et al., 2010; Parthier et al., 2007; Pioszak et al., 2008, 2009; Pioszak and Xu, 2008; Runge et al., 2008; Underwood et al., 2010) and a consensus has emerged from these studies. The peptides bind as extended α helices to the same region of the receptor, in a groove between the N and C termini of the isolated ECDs. For PTH, GIP, and GLP-1 families, the peptides are closest to the N terminus; for the CRF-related peptides, they are displaced to be closer to the C terminus."}
2_test
{"project":"2_test","denotations":[{"id":"25982113-15808821-71076097","span":{"begin":386,"end":390},"obj":"15808821"},{"id":"25982113-15808821-71076097","span":{"begin":386,"end":390},"obj":"15808821"},{"id":"25982113-21722971-118216083","span":{"begin":785,"end":789},"obj":"21722971"},{"id":"25982113-21722971-118216083","span":{"begin":785,"end":789},"obj":"21722971"},{"id":"25982113-20966082-118216084","span":{"begin":1079,"end":1083},"obj":"20966082"},{"id":"25982113-20966082-118216084","span":{"begin":1079,"end":1083},"obj":"20966082"},{"id":"25982113-17715056-118216085","span":{"begin":1102,"end":1106},"obj":"17715056"},{"id":"25982113-17715056-118216085","span":{"begin":1102,"end":1106},"obj":"17715056"},{"id":"25982113-18801728-118216086","span":{"begin":1124,"end":1128},"obj":"18801728"},{"id":"25982113-18801728-118216086","span":{"begin":1124,"end":1128},"obj":"18801728"},{"id":"25982113-19674967-118216087","span":{"begin":1130,"end":1134},"obj":"19674967"},{"id":"25982113-19674967-118216087","span":{"begin":1130,"end":1134},"obj":"19674967"},{"id":"25982113-18375760-118216088","span":{"begin":1152,"end":1156},"obj":"18375760"},{"id":"25982113-18375760-118216088","span":{"begin":1152,"end":1156},"obj":"18375760"},{"id":"25982113-18287102-118216089","span":{"begin":1172,"end":1176},"obj":"18287102"},{"id":"25982113-18287102-118216089","span":{"begin":1172,"end":1176},"obj":"18287102"},{"id":"25982113-19861722-118216090","span":{"begin":1196,"end":1200},"obj":"19861722"},{"id":"25982113-19861722-118216090","span":{"begin":1196,"end":1200},"obj":"19861722"},{"id":"T55104","span":{"begin":386,"end":390},"obj":"15808821"},{"id":"T68601","span":{"begin":386,"end":390},"obj":"15808821"},{"id":"25982113-21722971-71076098","span":{"begin":785,"end":789},"obj":"21722971"},{"id":"25982113-21722971-71076098","span":{"begin":785,"end":789},"obj":"21722971"},{"id":"25982113-20966082-71076099","span":{"begin":1196,"end":1200},"obj":"20966082"},{"id":"25982113-20966082-71076099","span":{"begin":1196,"end":1200},"obj":"20966082"},{"id":"25982113-17715056-71076099","span":{"begin":1196,"end":1200},"obj":"17715056"},{"id":"25982113-17715056-71076099","span":{"begin":1196,"end":1200},"obj":"17715056"},{"id":"25982113-18801728-71076099","span":{"begin":1196,"end":1200},"obj":"18801728"},{"id":"25982113-18801728-71076099","span":{"begin":1196,"end":1200},"obj":"18801728"},{"id":"25982113-19674967-71076099","span":{"begin":1196,"end":1200},"obj":"19674967"},{"id":"25982113-19674967-71076099","span":{"begin":1196,"end":1200},"obj":"19674967"},{"id":"25982113-18375760-71076099","span":{"begin":1196,"end":1200},"obj":"18375760"},{"id":"25982113-18375760-71076099","span":{"begin":1196,"end":1200},"obj":"18375760"},{"id":"25982113-18287102-71076099","span":{"begin":1196,"end":1200},"obj":"18287102"},{"id":"25982113-18287102-71076099","span":{"begin":1196,"end":1200},"obj":"18287102"},{"id":"25982113-19861722-71076099","span":{"begin":1196,"end":1200},"obj":"19861722"},{"id":"25982113-19861722-71076099","span":{"begin":1196,"end":1200},"obj":"19861722"}],"text":"G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that regulate a multitude of biological processes in response to a diverse array of stimuli and they are important drug targets. The class B/Secretin family GPCRs in humans include 15 receptors that are activated by diverse neuropeptides, peptide paracrine factors, and peptide endocrine hormones (Hoare, 2005). These receptors are less well understood than the larger class A/Rhodopsin family, despite their physiological and clinical importance. Class B GPCRs comprise an extracellular domain (ECD) of about 120 amino acids in addition to the 7-transmembrane (7TM) domain in the membrane. The ECD has an N-terminal α-helix and a set of β sheets held together by three disulfide bonds (Archbold et al., 2011). Peptides bind class B GPCRs via a “two-domain” model whereby their C-terminal region binds the ECD and their N-terminal region binds and activates the 7TM domain. Crystal structures are available for class B GPCR ECDs with bound peptides related to PTH, CRF, GIP, and GLP-1 (Pal et al., 2010; Parthier et al., 2007; Pioszak et al., 2008, 2009; Pioszak and Xu, 2008; Runge et al., 2008; Underwood et al., 2010) and a consensus has emerged from these studies. The peptides bind as extended α helices to the same region of the receptor, in a groove between the N and C termini of the isolated ECDs. For PTH, GIP, and GLP-1 families, the peptides are closest to the N terminus; for the CRF-related peptides, they are displaced to be closer to the C terminus."}