The first version of a glycoprotein hormone receptor (GPHR) information resource was designed to link functional with structural GPHR information, in order to support sequence-structure-function analysis of the LH, FSH, and TSH receptors (http://ssfa-gphr. tools to analyze the advanced structural features, with the common characteristics and distinctions between GPHRs, in a more exact manner. The hinge region with its second hormone-binding site allows us to assign practical data to the new structural features between hormone and receptor, such as binding details of a sulfated tyrosine (conserved throughout the GPHRs) extending into a pocket of the hormone. We have also implemented a protein interface analysis tool that enables the recognition and visualization of extracellular contact points between connection partners. This provides a starting point for comparing the binding patterns of GPHRs. Together with the mutagenesis data stored in the database, this will help to decipher the essential residues for ligand acknowledgement and the molecular mechanisms of transmission transduction, extending from your extracellular hormone-binding site toward the intracellular G protein-binding sites. The family of glycoprotein hormone receptors (GPHRs), a subgroup of the family A G protein-coupled receptors (GPCRs), consists of the YN968D1 TSH receptor (TSHR), the FSH receptor (FSHR), YN968D1 and the lutropin/choriogonadotropin receptor (LHCGR). The general YN968D1 structural topology of the homologous GPHRs is definitely identical with that of additional GPCRs and is characterized by an N-terminal extracellular region (N-ECR) and an intracellular C-terminal section, with 7-transmembrane helices (TMHs) connected by 3 intracellular loops and 3 extracellular loops. The TMHs and loops constitute the serpentine website or 7-transmembrane website (7-TMD), which spans the membrane from your extra- to the intracellular site. A special structural feature of all GPHRs, in contrast to additional family A GPCRs, is definitely a large N-ECR (Number 1A), which is made up of more than 320 amino acids (examined in Research 1). Number 1. Schematic Illustration of GPHR Topology and a Homology Model of hLHCGR N-ECR with Bound Lutropin. A, GPHRs possess a 7-TMH topology (serpentine website consists of 7-TMHs connected by 3 extracellular loops [ECLs] and 3 intercellular loops [ICLs]), as do … The major binding region for the hormones TSH, LH, chorionic gonadotropin (CG), and FSH (2) has been recognized by experimental studies within the LRRDs (3,C7). A complementary pattern of amino acid side-chain properties is YN968D1 responsible for specific hormone acknowledgement (8). Furthermore, the hinge region (comprising about 90C130 residues) has also been shown to be important for hormone binding and transmission induction (good examples in Referrals 9,C15). On the basis of site-directed mutagenesis, it has been concluded that the extracellular hinge region of GPHRs is necessary for stabilization of a signaling-competent basal receptor conformation (12, 15,C23), and it has been proposed the hinge region plays an important role in the rules and amplification of receptor activity (11, 16, 21, 24). The first crystal structure of the FSHR leucine-rich repeat domain (LRRD) complex with the hormone FSH (PDB [Protein Database] access code: 1XWD) was published Ly6a in 2005 (26). Moreover, the structural features of the FSHR LRRD were subsequently confirmed by crystal structure complexes between the TSHR LRRD and an activating (27) (PDB access code: 3G04) or inactivating (28) autoantibody (PDB access code: 2XWT), respectively. However, the detailed molecular mechanism of receptor activation and the rules of signaling activity in the extracellular site are not fully recognized. One major reason for this has been the lack of structural info for the hinge region containing the second hormone-binding site, which would be a prerequisite to clarify the exact set up of receptor parts to each other or to describe the entire hormone-binding process. This missing structural section was also absent in the freely available GPHR info source (web-address: http//:ssfa-gphr.de). This database and linked web applications were designed to collect relevant GPHR info, with the aim of assisting sequence-structure-function analysis (SSFA) of this GPCR subfamily (29). The SSFA-GPHR info resource allows a focused analysis of semiquantitative mutant data from GPHR subtypes and varied experimental methods (30, 31). A second and complementary GPHR info source with mutant data and several online applications has been provided by others (Research 32; http://gris.ulb.ac.be/). A new GPHR crystal structure (hFSHR in complex with hFSH) that is a milestone in GPHR study has recently been published (33). This structure presents structural information on almost the entire extracellular region, including the LRRD and most parts of the hinge region that had not yet been solved. Binding site analysis revealed that both the LRRD and the hinge region interact with the hormone. In result, combination of this novel structural info with available practical information allows us to answer important questions and to interpret experimental findings on GPHRs. For example, a section of the hinge region interacts directly with the hormone, and structural details of this second binding site can now become elucidated (33). This advanced info is also.
The first version of a glycoprotein hormone receptor (GPHR) information resource
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a 67 kDa type I transmembrane glycoprotein present on myeloid progenitors
and differentiation. The protein kinase family is one of the largest families of proteins in eukaryotes
Apoptosis
bladder
brain
breast
cell cycle progression
cervix
CSP-B
Cyproterone acetate
EGFR) is the prototype member of the type 1 receptor tyrosine kinases. EGFR overexpression in tumors indicates poor prognosis and is observed in tumors of the head and neck
EM9
endometrium
erythrocytes
F3
Goat polyclonal to IgG H+L)
Goat polyclonal to IgG H+L)Biotin)
GRK4
GSK1904529A
Igf1
Mapkap1
monocytes andgranulocytes. CD33 is absent on lymphocytes
Mouse monoclonal to CD33.CT65 reacts with CD33 andtigen
Palomid 529
platelets
PTK) or serine/threonine
Rabbit Polyclonal to ARNT.
Rabbit polyclonal to BMPR2
Rabbit Polyclonal to CCBP2.
Rabbit Polyclonal to EDG4
Rabbit polyclonal to EIF4E.
Rabbit polyclonal to IL11RA
Rabbit polyclonal to LRRIQ3
Rabbit Polyclonal to MCM3 phospho-Thr722)
Rabbit Polyclonal to RBM34
SB 216763
SKI-606
SNX-5422
STK) kinase catalytic domains. Epidermal Growth factor receptor
stomach
stomach and in squamous cell carcinoma.
TNFSF8
TSHR
VEGFA
vulva