Searchable abstracts of presentations at key conferences in endocrinology

ea0035p1081 | Thyroid (non-cancer) | ECE2014

Involvement of Lat2 in the transport of 3,3′-T2 across the plasma membrane and first structural insights into transport mechanisms by homology model generation

Kinne Anita , Hinz Katrin , Wittner Melanie , Krause Gerd

Thyroid hormones (THs) are transported into their target cells by diverse transmembrane transporter proteins, e.g. by members of the L-type amino acid transporter (LAT) family. The Lat2 is a sodium independent amino acid exchanger and interacts with CD98 for its efficient cell surface expression. So far the role of Lat2 in TH transport including the transport mechanisms is unclear. It is important to determine TH subtype specificity and to identify amino acids at Lat2 which ar...

ea0020p330 | Comparative Endocrinology | ECE2009

Comparative analyses between the glycoprotein-hormone receptors and the orphan leucine-rich repeat containing G-protein coupled receptor 4 (LGR4)

Kleinau Gunnar , Gruters Annette , Biebermann Heike , Krause Gerd

In recent decades intensive studies on the glycoprotein-hormone receptors (GPHRs) and their respective hormones have provided a number of molecular insights into the relationship between the structure and function of these proteins. This knowledge includes an understanding of hormone binding, of naturally occurring mutations nad mechanisms of signal transduction and G-protein binding processes.Together with the relaxin family peptide receptors (RxFP) the...

ea0020p681 | Signal Transduction | ECE2009

A newly identified loss-of-function mutation in helix 5 reveals new insights into signalling mechanisms of the thyrotropin receptor

Winkler Franziska , Kleinau Gunnar , Gruters Annette , Krude Heiko , Krause Gerd , Biebermann Heike

In two siblings suffering from congenital hypothyroidism we identified a homozygous missence mutation Ala579Val in transmembrane helix 5 of the thyrotropin receptor (TSHR) gene which motivated us to investigate molecular details of this mutation.We were interested, firstly, in the functional effects regarding signal transduction and, secondly, in the particular structural properties of the wild type receptor and the Ala579Val mutant. The aim was to gain ...

ea0016p653 | Signal transduction | ECE2008

The hinge region of the human TSH-receptor (hTSHR) mediates the activity of a superagonistic human TSH analog and bovine TSH

Mueller Sandra , Kleinau Gunnar , Skudlinski Mariusz , Jaeschke Holger , Krause Gerd , Paschke Ralf

The hinge region of the hTSHR links the extracellular LRR-domain with the transmembrane domain. Recently, we identified mutations E297A, E303A, and D382A in the hinge region with a cell surface expression comparable to the wt but with a strongly reduced bovine TSH (bTSH) binding. The combined triple mutation E297A/E303A/D382A revealed a cell surface expression comparable to the wt but in comparison to the single mutants a more pronounced reduction of bTSH binding (9% of the wt...

ea0014p609 | (1) | ECE2007

Implications for molecular mechanisms of glycoprotein hormone receptors using a new sequence-structure-function analysis resource

Kleinau Gunnar , Brehm Mara , Wiedemann Urs , Labudde Dirk , Leser Ulf , Krause Gerd

Comparison between wild type and mutated glycoprotein hormone receptors (GPHRs) TSHR, FSHR and LHCGR is established to identify determinants involved in molecular activation mechanism. The basic aims of current work are the discrimination of receptor phenotypes according the differences between activity states they represent and hit-assignment of classified phenotypes to 3D-structural positions to reveal functional-structural hotspots and interrelations between determinants th...

ea0070aep849 | Reproductive and Developmental Endocrinology | ECE2020

Aminoacidic residues discriminating human choriogonadotropin (hCG) and luteinizing hormone (LH) binding to the human receptor (LHCGR)

Lazzaretti Clara , Secco Valentina , Paradiso Elia , Sperduti Samantha , Rutz Claudia , Kreuchwig Annika , Krause Gerd , Simoni Manuela , Casarini Livio

The human luteinizing hormone (LH)/choriogonadotropin (hCG) receptor (LHCGR) discriminates its two hormone ligands. LHCGR differs to the murine receptor (Lhr) in aminoacid residues potentially involved in qualitative discerning of LH and hCG, the latter absent in rodents. We aim to identify LHCGR residues involved in hCG/LH discrimination, indicating evolutionary determinants of human LH/hCG endocrine system. After comparing the LHCGR and Lhr sequences, we developed eight ...

ea0032p577 | Female reproduction | ECE2013

The hinge region of the lutropin receptor mediates different activation mechanisms: CG induces trans- and LH only cis-initialization

Grzesik Paul , Kreuchwig Annika , Teichmann Anke , Furkert Jens , Rutz Claudia , Wiesner Burghard , Kleinau Gunnar , Schulein Ralf , Gromoll Jorg , Krause Gerd

The lutropin receptor (LHR) is associated with reproduction and becomes activated by choriogonadotropin (CG) or lutropin (LH) resulting in different physiological functions with regard to differing signaling cascades. The underlying mechanisms in receptor/hormone interaction are not yet understood. CG is known to induce trans-activation at LHR oligomers (activates a second receptor), but details of LH mechanisms were not clarified yet.To study this issue...

ea0086s4.1 | Old hormones, new tricks: new approaches for treating reproductive diseases | SFEBES2022

Size matters. Small molecule targeting of gonadotrophin hormone receptors

Hanyroup Sharika , Anderson Ross , Nataraja Selvaraj , Yu Henry , Kreuchwig Annika , Krause Gerd , Katz Arieh , Millar Robert , Newton Claire

G protein-coupled receptors (GPCRs) are critical for signal transduction within neuroendocrine signalling pathways, and genetic mutations in G protein-coupled GPCRs underlie numerous diseases. Inactivating GPCR mutations can impede ligand interactions or signal transduction, or can result in misfolding of nascent receptor proteins and subsequent retention in the endoplasmic reticulum (ER) and thus failure to traffic to the cell surface. Examination of the functionality and cel...

ea0016p538 | Obesity | ECE2008

Molecular insights in dysfunctions of the human melanocortin-4-receptor (MC4R) caused by mutations in the third transmembrane domain (TM3) and the second intracellular loop

Tarnow Patrick , Rediger Anne , Widhalm Kurt , Friedel Susann , Kleinau Gunnar , Bolz Hanno , Bettecken Thomas , Hinney Anke , Krause Gerd , Gruters Annette , Biebermann Heike

Mutations in the hypothalamic expressed MC4R gene are the most frequent cause of monogenetic obesity. This Gαs-Protein coupled receptor (GPCR) is activated by endogenous ligands α- and β-MSH and is inhibited by the only known endogenous inverse agonist and antagonist Agouti related peptide (AgRP). Naturally occurring mutations help to understand activation mechanisms of the human MC4R.We previously described a constitutively act...