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PDBsum entry 1xul

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protein Protein-protein interface(s) links
Complex (hormone/receptor) PDB id
1xul
Jmol PyMol
Contents
Protein chains
85 a.a.
110 a.a.
182 a.a.
Theoretical model
PDB id:
1xul
Name: Complex (hormone/receptor)
Title: Theoretical model of the ligand-binding region of lutropin receptor complexed with human chorionic gonadotropin
Structure: Chorionic gonadotropin. Chain: a, b. Lutropin receptor. Chain: c. Fragment: residues 51 - 232. Synonym: human chorionic gonadotropin receptor
Source: Homo sapiens. Human. Human
Authors: X.Jiang,M.Dreano,D.R.Buckler,S.Cheng,A.Ythier,H.Wu, W.A.Hendrickson,N.El Tayar
Key ref:
X.Jiang et al. (1995). Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions. Structure, 3, 1341-1353. PubMed id: 8747461 DOI: 10.1016/S0969-2126(01)00272-6
Date:
27-Dec-96     Release date:   15-May-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01215  (GLHA_HUMAN) -  Glycoprotein hormones alpha chain
Seq:
Struc:
116 a.a.
87 a.a.
Protein chain
Pfam   ArchSchema ?
P01233  (CGHB_HUMAN) -  Choriogonadotropin subunit beta
Seq:
Struc:
165 a.a.
110 a.a.
Protein chain
Pfam   ArchSchema ?
P22888  (LSHR_HUMAN) -  Lutropin-choriogonadotropic hormone receptor
Seq:
Struc:
 
Seq:
Struc:
699 a.a.
182 a.a.
Key:    PfamA domain  Secondary structure

 

 
DOI no: 10.1016/S0969-2126(01)00272-6 Structure 3:1341-1353 (1995)
PubMed id: 8747461  
 
 
Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions.
X.Jiang, M.Dreano, D.R.Buckler, S.Cheng, A.Ythier, H.Wu, W.A.Hendrickson, N.el Tayar.
 
  ABSTRACT  
 
BACKGROUND: Glycoprotein hormones influence the development and function of the ovary, testis and thyroid by binding to specific high-affinity receptors. The extracellular domains of these receptors are members of the leucine-rich repeat (LRR) protein superfamily and are responsible for the high-affinity binding. The crystal structure of a glycoprotein hormone, namely human choriogonadotropin (hCG), is known, but neither the receptor structure, mode of hormone binding, nor mechanism for activation, have been established. RESULTS: Despite very low sequence similarity between exon-demarcated LRRs in the receptors and the LRRs of porcine ribonuclease inhibitor (RI), the secondary structures for the two repeat sets are found to be alike Constraints on curvature and beta-barrel geometry from the sequence pattern for repeated beta alpha units suggest that the receptors contain three-dimensional structures similar to that of RI. With the RI crystal structure as a template, models were constructed for exons 2-8 of the receptors. The model for this portion of the choriogonadotropin receptor is complementary in shape and electrostatic characteristics to the surface of hCG at an identified focus of hormone-receptor interaction. CONCLUSIONS: The predicted models for the structures and mode of hormone binding of the glycoprotein hormone receptors are to a large extent consistent with currently available biochemical and mutational data. Repeated sequences in beta-barrel proteins are shown to have general implications for constraints on structure. Averaging techniques used here to recognize the structural motif in these receptors should also apply to other proteins with repeated sequences.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. . Representative β-barrel structures shown as unrolled sheets: (a) ribonuclease inhibitor, RI; (b) triose phosphate isomerase, TIM; and (c) the human rhinovirus (HRV) pentamer from the icosahedral fivefold axes. In each case, the barrel axis is vertical and the view is from inside of the barrel. Residues are identified by the single letter code on open circles for side chains that point into the barrel interior and by filled circles for those that point away (toward the α helices in the case of RI and TIM). RI, TIM and HRV are examples of cases with shear per strand, S/N, of 0, 1 and 2 and strand inclinations of 0°, 36° and 55°, respectively. Figure 3. . Representative β-barrel structures shown as unrolled sheets: (a) ribonuclease inhibitor, RI; (b) triose phosphate isomerase, TIM; and (c) the human rhinovirus (HRV) pentamer from the icosahedral fivefold axes. In each case, the barrel axis is vertical and the view is from inside of the barrel. Residues are identified by the single letter code on open circles for side chains that point into the barrel interior and by filled circles for those that point away (toward the α helices in the case of RI and TIM). RI, TIM and HRV are examples of cases with shear per strand, S/N, of 0, 1 and 2 and strand inclinations of 0°, 36° and 55°, respectively.
Figure 6.
Figure 6. . Electrostatic potential on the solvent-accessible surface of hCG and LHR. (a) Front view of hCG showing the binding surface. (b) Back view of hCG. (c) Front view of LHR showing the inner surface. (d) Back view of LHR showing the outer surface. The front and back views of each are related by 180° rotation along a vertical axis. Negative potential is colored red and positive potential, blue, with greatest saturations at ± 10 kT, respectively. (The figure was generated using the program GRASP [72].). Figure 6. . Electrostatic potential on the solvent-accessible surface of hCG and LHR. (a) Front view of hCG showing the binding surface. (b) Back view of hCG. (c) Front view of LHR showing the inner surface. (d) Back view of LHR showing the outer surface. The front and back views of each are related by 180° rotation along a vertical axis. Negative potential is colored red and positive potential, blue, with greatest saturations at ± 10 kT, respectively. (The figure was generated using the program GRASP [[3]72].).
 
  The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 1341-1353) copyright 1995.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17059864 D.Puett, Y.Li, G.DeMars, K.Angelova, and F.Fanelli (2007).
A functional transmembrane complex: the luteinizing hormone receptor with bound ligand and G protein.
  Mol Cell Endocrinol, 260, 126-136.  
17045735 Q.R.Fan, and W.A.Hendrickson (2007).
Assembly and structural characterization of an authentic complex between human follicle stimulating hormone and a hormone-binding ectodomain of its receptor.
  Mol Cell Endocrinol, 260, 73-82.  
17143726 S.R.Setlur, and R.R.Dighe (2007).
Single chain human chorionic gonadotropin, hCGalphabeta: effects of mutations in the alpha subunit on structure and bioactivity.
  Glycoconj J, 24, 97.  
17059863 W.Lin, M.P.Bernard, D.Cao, R.V.Myers, J.E.Kerrigan, and W.R.Moyle (2007).
Follitropin receptors contain cryptic ligand binding sites.
  Mol Cell Endocrinol, 260, 83-92.  
16467256 D.Puett, Y.Li, K.Angelova, G.Demars, T.P.Meehan, F.Fanelli, and P.Narayan (2005).
Structure-function relationships of the luteinizing hormone receptor.
  Ann N Y Acad Sci, 1061, 41-54.  
20035466 J.Bogerd (2005).
Selective ligand-binding determinants in catfish and human gonadotropin receptors.
  Fish Physiol Biochem, 31, 247-254.  
16316453 P.S.Kene, D.V.Behere, and S.D.Mahale (2005).
Secondary structure analysis of synthetic peptides of the extracellular domain of the human follicle-stimulating hormone receptor.
  J Pept Res, 66, 375-381.  
  15948771 P.S.Kene, R.R.Dighe, and S.D.Mahale (2005).
Delineation of regions in the extracellular domain of follicle-stimulating hormone receptor involved in hormone binding and signal transduction.
  Am J Reprod Immunol, 54, 38-48.  
15662415 Q.R.Fan, and W.A.Hendrickson (2005).
Structure of human follicle-stimulating hormone in complex with its receptor.
  Nature, 433, 269-277.
PDB code: 1xwd
14757772 A.Shimizu, T.Matsushita, T.Kondo, Y.Inden, T.Kojima, H.Saito, and M.Hirai (2004).
Identification of the amino acid residues of the platelet glycoprotein Ib (GPIb) essential for the von Willebrand factor binding by clustered charged-to-alanine scanning mutagenesis.
  J Biol Chem, 279, 16285-16294.  
15345720 G.Kleinau, H.Jäschke, S.Neumann, J.Lättig, R.Paschke, and G.Krause (2004).
Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface.
  J Biol Chem, 279, 51590-51600.  
15304512 M.P.Bernard, W.Lin, D.Cao, R.V.Myers, Y.Xing, and W.R.Moyle (2004).
Only a portion of the small seatbelt loop in human choriogonadotropin appears capable of contacting the lutropin receptor.
  J Biol Chem, 279, 44438-44441.  
14581462 P.M.Apaja, K.T.Harju, J.T.Aatsinki, U.E.Petäjä-Repo, and H.J.Rajaniemi (2004).
Identification and structural characterization of the neuronal luteinizing hormone receptor associated with sensory systems.
  J Biol Chem, 279, 1899-1906.  
15650352 R.Núñez Miguel, J.Sanders, J.Jeffreys, H.Depraetere, M.Evans, T.Richards, T.L.Blundell, B.Rees Smith, and J.Furmaniak (2004).
Analysis of the thyrotropin receptor-thyrotropin interaction by comparative modeling.
  Thyroid, 14, 991.  
15304493 W.R.Moyle, Y.Xing, W.Lin, D.Cao, R.V.Myers, J.E.Kerrigan, and M.P.Bernard (2004).
Model of glycoprotein hormone receptor ligand binding and signaling.
  J Biol Chem, 279, 44442-44459.  
12773385 G.Smits, M.Campillo, C.Govaerts, V.Janssens, C.Richter, G.Vassart, L.Pardo, and S.Costagliola (2003).
Glycoprotein hormone receptors: determinants in leucine-rich repeats responsible for ligand specificity.
  EMBO J, 22, 2692-2703.  
12598521 H.F.Vischer, J.C.Granneman, M.J.Noordam, S.Mosselman, and J.Bogerd (2003).
Ligand selectivity of gonadotropin receptors. Role of the beta-strands of extracellular leucine-rich repeats 3 and 6 of the human luteinizing hormone receptor.
  J Biol Chem, 278, 15505-15513.  
12963710 J.Sohn, H.Youn, M.Jeoung, Y.Koo, C.Yi, I.Ji, and T.H.Ji (2003).
Orientation of follicle-stimulating hormone (FSH) subunits complexed with the FSH receptor. Beta subunit toward the N terminus of exodomain and alpha subunit to exoloop 3.
  J Biol Chem, 278, 47868-47876.  
12506116 S.Sudo, J.Kumagai, S.Nishi, S.Layfield, T.Ferraro, R.A.Bathgate, and A.J.Hsueh (2003).
H3 relaxin is a specific ligand for LGR7 and activates the receptor by interacting with both the ectodomain and the exoloop 2.
  J Biol Chem, 278, 7855-7862.  
11967365 A.V.Kajava, and B.Kobe (2002).
Assessment of the ability to model proteins with leucine-rich repeats in light of the latest structural information.
  Protein Sci, 11, 1082-1090.  
12070159 K.Angelova, F.Fanelli, and D.Puett (2002).
A model for constitutive lutropin receptor activation based on molecular simulation and engineered mutations in transmembrane helices 6 and 7.
  J Biol Chem, 277, 32202-32213.  
11847099 S.Costagliola, V.Panneels, M.Bonomi, J.Koch, M.C.Many, G.Smits, and G.Vassart (2002).
Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors.
  EMBO J, 21, 504-513.  
11591722 Y.Xing, W.Lin, M.Jiang, R.V.Myers, D.Cao, M.P.Bernard, and W.R.Moyle (2001).
Alternatively folded choriogonadotropin analogs. Implications for hormone folding and biological activity.
  J Biol Chem, 276, 46953-46960.  
10899142 K.K.Eriksen, F.Hauser, M.Schiøtt, K.M.Pedersen, L.Søndergaard, and C.J.Grimmelikhuijzen (2000).
Molecular cloning, genomic organization, developmental regulation, and a knock-out mutant of a novel leu-rich repeats-containing G protein-coupled receptor (DLGR-2) from Drosophila melanogaster.
  Genome Res, 10, 924-938.  
10992290 M.T.Hearn, and P.T.Gomme (2000).
Molecular architecture and biorecognition processes of the cystine knot protein superfamily: part I. The glycoprotein hormones.
  J Mol Recognit, 13, 223-278.  
10820024 M.T.Vu-Hai, J.C.Huet, K.Echasserieau, J.M.Bidart, C.Floiras, J.C.Pernollet, and E.Milgrom (2000).
Posttranslational modifications of the lutropin receptor: mass spectrometric analysis.
  Biochemistry, 39, 5509-5517.  
10913841 R.V.Myers, Y.Wang, and W.R.Moyle (2000).
The surface of alpha-subunit loop 1 distant from the subunit interface is exposed in the hCG lutropin receptor complex.
  Biochim Biophys Acta, 1475, 390-394.  
10438509 J.B.Janosi, P.A.Ramsland, M.R.Mott, S.M.Firth, R.C.Baxter, and P.J.Delhanty (1999).
The acid-labile subunit of the serum insulin-like growth factor-binding protein complexes. Structural determination by molecular modeling and electron microscopy.
  J Biol Chem, 274, 23328-23332.  
9800204 C.M.Thomas, M.S.Dixon, M.Parniske, C.Golstein, and J.D.Jones (1998).
Genetic and molecular analysis of tomato Cf genes for resistance to Cladosporium fulvum.
  Philos Trans R Soc Lond B Biol Sci, 353, 1413-1424.  
9783912 F.P.Zhang, J.Kero, and I.Huhtaniemi (1998).
The unique exon 10 of the human luteinizing hormone receptor is necessary for expression of the receptor protein at the plasma membrane in the human luteinizing hormone receptor, but deleterious when inserted into the human follicle-stimulating hormone receptor.
  Mol Cell Endocrinol, 142, 165-174.  
9558473 M.L.Dufau (1998).
The luteinizing hormone receptor.
  Annu Rev Physiol, 60, 461-496.  
9593728 S.Hong, T.Phang, I.Ji, and T.H.Ji (1998).
The amino-terminal region of the luteinizing hormone/choriogonadotropin receptor contacts both subunits of human choriogonadotropin. I. Mutational analysis.
  J Biol Chem, 273, 13835-13840.  
9593729 T.Phang, G.Kundu, S.Hong, I.Ji, and T.H.Ji (1998).
The amino-terminal region of the luteinizing hormone/choriogonadotropin receptor contacts both subunits of human choriogonadotropin. II. Photoaffinity labeling.
  J Biol Chem, 273, 13841-13847.  
8995395 F.Hauser, H.P.Nothacker, and C.J.Grimmelikhuijzen (1997).
Molecular cloning, genomic organization, and developmental regulation of a novel receptor from Drosophila melanogaster structurally related to members of the thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone/choriogonadotropin receptor family from mammals.
  J Biol Chem, 272, 1002-1010.  
9013570 L.Cosowsky, W.Lin, Y.Han, M.P.Bernard, R.K.Campbell, and W.R.Moyle (1997).
Influence of subunit interactions on lutropin specificity. Implications for studies of glycoprotein hormone function.
  J Biol Chem, 272, 3309-3314.  
9284286 N.Grewal, S.Nagpal, G.B.Chavali, S.S.Majumdar, R.Pal, and D.M.Salunke (1997).
Ligand-induced receptor dimerization may be critical for signal transduction by choriogonadotropin.
  Biophys J, 73, 1190-1197.  
9160749 S.E.Clark, R.W.Williams, and E.M.Meyerowitz (1997).
The CLAVATA1 gene encodes a putative receptor kinase that controls shoot and floral meristem size in Arabidopsis.
  Cell, 89, 575-585.  
9312107 Y.Osuga, M.Hayashi, M.Kudo, M.Conti, B.Kobilka, and A.J.Hsueh (1997).
Co-expression of defective luteinizing hormone receptor fragments partially reconstitutes ligand-induced signal generation.
  J Biol Chem, 272, 25006-25012.  
8946845 B.Kobe (1996).
Leucines on a roll.
  Nat Struct Biol, 3, 977-980.  
8940183 C.Wu, P.Narayan, and D.Puett (1996).
Protein engineering of a novel constitutively active hormone-receptor complex.
  J Biol Chem, 271, 31638-31642.  
9027343 D.Puett, N.Bhowmick, L.M.Fernandez, J.Huang, C.Wu, and P.Narayan (1996).
hCG-receptor binding and transmembrane signaling.
  Mol Cell Endocrinol, 125, 55-64.  
9027346 J.J.Remy, L.Couture, J.Pantel, T.Haertlé, H.Rabesona, V.Bozon, E.Pajot-Augy, P.Robert, F.Troalen, R.Salesse, and J.M.Bidart (1996).
Mapping of HCG-receptor complexes.
  Mol Cell Endocrinol, 125, 79-91.  
8917465 L.Couture, J.J.Remy, H.Rabesona, F.Troalen, E.Pajot-Augy, V.Bozon, T.Haertle, J.M.Bidart, and R.Salesse (1996).
A defined epitope on the human choriogonadotropin alpha-subunit interacts with the second extracellular loop of the transmembrane domain of the lutropin/choriogonadotropin receptor.
  Eur J Biochem, 241, 627-632.  
9631089 M.W.Szkudlinski, N.G.Teh, M.Grossmann, J.E.Tropea, and B.D.Weintraub (1996).
Engineering human glycoprotein hormone superactive analogues.
  Nat Biotechnol, 14, 1257-1263.  
9027344 N.el Tayar (1996).
Advances in the molecular understanding of gonadotropins-receptors interactions.
  Mol Cell Endocrinol, 125, 65-70.  
9027341 P.Berger, J.M.Bidart, P.S.Delves, S.Dirnhofer, R.Hoermann, N.Isaacs, A.Jackson, T.Klonisch, A.Lapthorn, T.Lund, K.Mann, I.Roitt, S.Schwarz, and G.Wick (1996).
Immunochemical mapping of gonadotropins.
  Mol Cell Endocrinol, 125, 33-43.  
9631081 R.W.Ruddon (1996).
Super hormones.
  Nat Biotechnol, 14, 1224.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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