Abstract:
:The receptor tyrosine kinase superfamily comprises many cell-surface receptors including the insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF1R) that are constitutively homodimeric transmembrane glycoproteins. Therefore, these receptors require ligand-triggered domain rearrangements rather than receptor dimerization for activation. Specifically, binding of peptide ligands to receptor ectodomains transduces signals across the transmembrane domains for trans-autophosphorylation in cytoplasmic kinase domains. The molecular details of these processes are poorly understood in part due to the absence of structures of full-length receptors. Using MD simulations and enhanced conformational sampling algorithms, we present all-atom structural models of peptides containing 51 residues from the transmembrane and juxtamembrane regions of IR and IGF1R. In our models, the transmembrane regions of both receptors adopt helical conformations with kinks at Pro961 (IR) and Pro941 (IGF1R), but the C-terminal residues corresponding to the juxtamembrane region of each receptor adopt unfolded and flexible conformations in IR as opposed to a helix in IGF1R. We also observe that the N-terminal residues in IR form a kinked-helix sitting at the membrane-solvent interface, while homologous residues in IGF1R are unfolded and flexible. These conformational differences result in a larger tilt-angle of the membrane-embedded helix in IGF1R in comparison to IR to compensate for interactions with water molecules at the membrane-solvent interfaces. Our metastable/stable states for the transmembrane domain of IR, observed in a lipid bilayer, are consistent with a known NMR structure of this domain determined in detergent micelles, and similar states in IGF1R are consistent with a previously reported model of the dimerized transmembrane domains of IGF1R. Our all-atom structural models suggest potentially unique structural organization of kinase domains in each receptor.
journal_name
Front Endocrinol (Lausanne)journal_title
Frontiers in endocrinologyauthors
Mohammadiarani H,Vashisth Hdoi
10.3389/fendo.2016.00068subject
Has Abstractpub_date
2016-06-20 00:00:00pages
68issn
1664-2392journal_volume
7pub_type
杂志文章abstract::Besides its interest for diagnosis, the finding of an elevated serum AMH level in PCOS has open major pathophysiological issues. This review addresses the three most important issues: 1- the role of AMH in the disturbed folliculogenesis of PCOS; 2- the role of AMH in the gonadotropin dysregulation of PCOS and 3- the r...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00641
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abstract::In addition to the obvious differences in body shape, there are substantial differences in lipid metabolism between men and women. These differences include how dietary fatty acids are handled, the secretion and clearance of very low-density lipoprotein-triglycerides, the release rates of free fatty acids (FFA) from a...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2015.00103
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doi:10.3389/fendo.2020.00115
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2015.00081
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abstract::Brown adipose tissue (BAT) non-shivering thermogenesis impacts energy homeostasis in rodents and humans. Mitochondrial uncoupling protein 1 in brown fat cells produces heat by dissipating the energy generated by fatty acid and glucose oxidation. In addition to thermogenesis and despite its small relative size, sympath...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2011.00084
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abstract::The Twist proteins (Twist-1 and -2) are highly conserved developmental proteins with key roles for the transcriptional regulation in mesenchymal cell lineages. They belong to the super-family of bHLH proteins and exhibit bi-functional roles as both activators and repressors of gene transcription. The Twist proteins ar...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2012.00108
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abstract:Objective:To evaluate whether endometrial thickness (EMT) change in response to progesterone has an effect on pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles. Design:Retrospective observational study. Setting:Tertiary-care academic medical center. Participants:4465 infertile women undergoing their f...
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doi:10.3389/fendo.2020.546232
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abstract::Introduction: To improve detection of undiagnosed diabetes in Africa, there is movement to replace the OGTT with A1C. The performance of A1C in the absence of hemoglobin-related micronutrient deficiencies, anemia and heterozygous hemoglobinopathies is unknown. Therefore, we determined in 441 African-born blacks living...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00533
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2016.00047
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abstract::The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) - secreted by the placenta, and lutropin (LH) - produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2015.00140
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00152
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abstract::Non-alcoholic fatty liver disease (NAFLD) is common in patients with growth hormone deficiency (GHD). Some noninvasive techniques have been used to quantify liver fat, such as the controlled attenuation parameter (CAP). Objective: To evaluate CAP as a tool to identify liver steatosis and its relationship with differen...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00364
更新日期:2019-06-19 00:00:00
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2015.00155
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abstract::Background: This meta-analysis aims to evaluate the long-term efficacy of medication treatment vs. surgery treatment in patients with prolactinomas. Methods: An electronic literature search was performed using MEDLINE, EMBASE and Web of Science databases for studies dated before July in 2018. Patients with prolactinom...
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pub_type: 杂志文章
doi:10.3389/fendo.2018.00636
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.601745
更新日期:2020-11-26 00:00:00
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00297
更新日期:2020-06-03 00:00:00
abstract::Background: Bologna criteria poor ovarian responders have a very low prognosis. Although, it has been proposed that LH supplementation could be beneficial in women with previous hypo-response to FSH. There are no studies comparing the cumulative live birth rates (LBRs) between corifollitropin alfa (CFA) and highly pur...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00175
更新日期:2019-03-22 00:00:00
abstract::During mammalian pregnancy, highly specialized mechanisms of immune tolerance are triggered in order to allow the semi-allogeneic fetus to grow within the maternal uterus in harmony with the maternal immune system. Among other mechanisms, changes in the endocrine status have been proposed to be at least part of the ma...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2014.00039
更新日期:2014-04-01 00:00:00
abstract::Fibroblast growth factor 1 (FGF1) is reported to be expressed in the testis. How FGF1 affects stem Leydig cell development remains unclear. Here, we report the effects of FGF1 on rat stem Leydig cell development in an ethane dimethane sulfonate (EDS)-treated model. FGF1 (100 ng/testis) significantly increased serum te...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2012.00148
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2016.00077
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journal_title:Frontiers in endocrinology
pub_type:
doi:10.3389/fendo.2018.00723
更新日期:2018-12-17 00:00:00
abstract::Anaplastic thyroid cancer is known to be the most lethal malignancy among endocrine tumors for its extremely limited survival rate after diagnosis. As a result of this poor survival prognosis, multimodal therapy is currently under investigation to address this global concern. In this reported case, the 125I seed impla...
journal_title:Frontiers in endocrinology
pub_type:
doi:10.3389/fendo.2020.00207
更新日期:2020-04-22 00:00:00
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2017.00059
更新日期:2017-03-31 00:00:00
abstract::Introduction: Adrenal myelolipomas are usually isolated benign adrenal lesions, but can be adjacent to steroid-secreting adrenocortical tumors. We studied the aberrant regulation of cortisol secretion in a 61 year-old woman with combined bilateral myelolipomas and primary bilateral macronodular adrenal hyperplasia (BM...
journal_title:Frontiers in endocrinology
pub_type:
doi:10.3389/fendo.2019.00618
更新日期:2019-09-11 00:00:00
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2016.00138
更新日期:2016-10-20 00:00:00
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00827
更新日期:2019-12-05 00:00:00
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00601
更新日期:2018-10-15 00:00:00
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journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.586352
更新日期:2020-11-09 00:00:00
abstract::Insulin-like growth factor-binding proteins (IGFBPs) are multifunctional proteins that possess IGF-dependent and -independent actions. Recent studies suggest that its IGF-independent action appeared early and that the IGF-binding function may have been acquired later in evolution. The timing of the emergence of IGF-de...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2016.00174
更新日期:2017-01-18 00:00:00