کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8478261 | 1550999 | 2007 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A functional transmembrane complex: The luteinizing hormone receptor with bound ligand and G protein
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کلمات کلیدی
LHRHEKECDTSHLRRGPCRTSHRFSHRHCG - اچ سی جیEctodomain - اکتودومینleucine-rich repeat - تکرار غنی از لوسینCoupling efficiency - راندمان اتصالlow density lipoprotein - لیپوپروتئین چگالی کمLDL - لیپوپروتئین کم چگالی(کلسترول بد)wild type - نوع وحشیfollicle stimulating hormone - هورمون تحریک کننده فولیکولluteinizing hormone - هورمون جسم زردthyroid stimulating hormone - هورمون محرک تیروئیدFSH - هورمون محرکه فولیکولی Gs protein - پروتئین Gshuman embryonic kidney - کلیه جنین انسانchorionic gonadotropin - گونادوتروپین کوریونیhuman chorionic gonadotropin - گونادوتروپین کوریونی انسانFSH receptor - گیرنده FSHLH receptor - گیرنده LHTSH receptor - گیرنده TSHglycoprotein hormone receptor - گیرنده هورمون گلیکوپروتئینG protein-coupled receptor - گیرندههای جفتشونده با پروتئین جی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The luteinizing hormone receptor (LHR) is one of eight members in a cluster of the rhodopsin family of the large G protein-coupled receptor (GPCR) superfamily that contains some 800-900 genes in the human genome. LHR, along with its paralogons, follicle stimulating hormone receptor (FSHR) and thyroid stimulating hormone receptor, form one of the three classes in this cluster; the two other classes contain the relaxin-binding GPCRs and orphan GPCRs. These GPCRs are characterized by a relatively large ectodomain (ECD) containing leucine-rich-repeats (LRRs); in the class of glycoprotein hormone receptors, the LRR region is capped by N-terminal and C-terminal cysteine-rich regions. Binding of human chorionic gonadotropin (hCG) or luteinizing hormone to the LHR-ECD triggers a conformational change of the transmembrane region of the receptor facilitating binding and activation of Gs, followed by effector enzyme activation and subsequent intracellular signaling. Viewing LHR as a transmembrane anchoring protein that sequentially binds hCG and Gs to give the hCG-LHR-Gs complex, numerous interactions and conformational changes must be considered. There is, unfortunately, a paucity of structural data on LHR, but crystal structures exist for hCG, the homologous FSH-FSHR-ECD (N-terminal fragment) complex, rhodopsin (in the inactive state), an active form of Gαs (transducin), and the βγ heterodimer. Using a combined experimental (site-directed mutagenesis followed by characterization in transfected cells) and computational (homology modeling and molecular dynamics simulations) approach, good working models are being developed for the protein-protein interaction faces and, in some cases, the ensuing conformational changes induced by complex formation. hCG binding to the LHR-ECD appears to involve several LRRs; LHR activation can be described in terms of disrupting a network of H-bonds in the cytosolic halves of helices 1-3, 6, and 7; and binding of LHR to Gs involves, in large part, intracellular loop 2 binding, presumably to Gsα at its C-terminus. Major gaps exist in our understanding at the molecular level of the six-polypeptide chain complex, hCG-LHR-Gs, but considerable progress has been made in the past few years.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volumes 260â262, 2 January 2007, Pages 126-136
Journal: Molecular and Cellular Endocrinology - Volumes 260â262, 2 January 2007, Pages 126-136
نویسندگان
D. Puett, Y. Li, G. DeMars, K. Angelova, F. Fanelli,