spacer
spacer
Go to PDB code: 
protein Protein-protein interface(s) links
Transferase PDB id
1s4y
Jmol
Contents
Protein chains
91 a.a. *
111 a.a. *
96 a.a. *
Waters ×177
* Residue conservation analysis
PDB id:
1s4y
Name: Transferase
Title: Crystal structure of the activin/actriib extracellular domai
Structure: Activin receptor type iib precursor. Chain: a, c. Fragment: extracellular domain. Synonym: actr-iib. Engineered: yes. Inhibin beta a chain. Chain: b, d. Synonym: activin beta-a chain, erythroid differentiation pr edf.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: acvr2b. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
Biol. unit: Tetramer (from PQS)
Resolution:
2.30Å     R-factor:   0.210     R-free:   0.286
Authors: J.Greenwald,M.E.Vega,G.P.Allendorph,W.H.Fischer,W.Vale,S.Cho Center For Structural Genomics (Jcsg)
Key ref:
J.Greenwald et al. (2004). A flexible activin explains the membrane-dependent cooperative assembly of TGF-beta family receptors. Mol Cell, 15, 485-489. PubMed id: 15304227 DOI: 10.1016/j.molcel.2004.07.011
Date:
19-Jan-04     Release date:   10-Aug-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P27040  (AVR2B_MOUSE) -  Activin receptor type-2B
Seq:
Struc: 		 
Seq:
Struc: 		536 a.a.
91 a.a.
Protein chain
Pfam   ArchSchema ?
P08476  (INHBA_HUMAN) -  Inhibin beta A chain
Seq:
Struc: 		426 a.a.
111 a.a.
Protein chain
Pfam   ArchSchema ?
P08476  (INHBA_HUMAN) -  Inhibin beta A chain
Seq:
Struc: 		426 a.a.
96 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, C: E.C.2.7.11.30  - Receptor protein serine/threonine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + [receptor-protein] = ADP + [receptor-protein] phosphate
ATP
 + [receptor-protein]
 = ADP
 + [receptor-protein] phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     transmembrane receptor protein serine/threonine kinase signaling pathway   1 term 
  Biochemical function     growth factor activity     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.molcel.2004.07.011 Mol Cell 15:485-489 (2004)
PubMed id: 15304227  
 
 
A flexible activin explains the membrane-dependent cooperative assembly of TGF-beta family receptors.
J.Greenwald, M.E.Vega, G.P.Allendorph, W.H.Fischer, W.Vale, S.Choe.
 
  ABSTRACT  
 
A new crystal structure of activin in complex with the extracellular domain of its type II receptor (ActRIIb-ECD) shows that the ligand exhibits an unexpected flexibility. The motion in the activin dimer disrupts its type I receptor interface, which may account for the disparity in its affinity for type I versus type II receptors. We have measured the affinities of activin and its antagonist inhibin for ActRIIb-ECD and found that the affinity of the 2-fold symmetric homodimer activin for ActRIIb-ECD depends on the availability of two spatially coupled ActRIIb-ECD molecules, whereas the affinity of the heterodimer inhibin does not. Our results indicate that activin's affinity for its two receptor types is greatly influenced by their membrane-restricted setting. We propose that activin affinity is modulated by the ligand flexibility and that cooperativity is achieved by binding to two ActRII chains that immobilize activin in a type I binding-competent orientation.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Ligand Flexibility for Receptor Assembly in the Membrane 		Figure 3.
Figure 3. The 1:1 Stoichiometry of the Complex Formed between Inhibin and ActRIIb-ECD
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2004, 15, 485-489) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20629020 L.Calvanese, D.Marasco, N.Doti, A.Saporito, G.D'Auria, L.Paolillo, M.Ruvo, and L.Falcigno (2010).
Structural investigations on the Nodal-Cripto binding: a theoretical and experimental approach.
  Biopolymers, 93, 1011-1021.  
19457927 C.Belville, J.D.Maréchal, S.Pennetier, P.Carmillo, L.Masgrau, L.Messika-Zeitoun, J.Galey, G.Machado, D.Treton, J.Gonzalès, J.Y.Picard, N.Josso, R.L.Cate, and N.di Clemente (2009).
Natural mutations of the anti-Mullerian hormone type II receptor found in persistent Mullerian duct syndrome affect ligand binding, signal transduction and cellular transport.
  Hum Mol Genet, 18, 3002-3013.  
19644449 J.N.Cash, C.A.Rejon, A.C.McPherron, D.J.Bernard, and T.B.Thompson (2009).
The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding.
  EMBO J, 28, 2662-2676.
PDB code: 3hh2
19926516 J.Nickel, W.Sebald, J.C.Groppe, and T.D.Mueller (2009).
Intricacies of BMP receptor assembly.
  Cytokine Growth Factor Rev, 20, 367-377.  
19735544 K.Heinecke, A.Seher, W.Schmitz, T.D.Mueller, W.Sebald, and J.Nickel (2009).
Receptor oligomerization and beyond: a case study in bone morphogenetic proteins.
  BMC Biol, 7, 59.  
19273500 Y.Xia, and A.L.Schneyer (2009).
The biology of activin: recent advances in structure, regulation and function.
  J Endocrinol, 202, 1.  
18485004 A.Galat, G.Gross, P.Drevet, A.Sato, and A.Ménez (2008).
Conserved structural determinants in three-fingered protein domains.
  FEBS J, 275, 3207-3225.  
18089557 J.A.Kelber, G.Shani, E.C.Booker, W.W.Vale, and P.C.Gray (2008).
Cripto is a noncompetitive activin antagonist that forms analogous signaling complexes with activin and nodal.
  J Biol Chem, 283, 4490-4500.  
18768470 R.Stamler, H.T.Keutmann, Y.Sidis, C.Kattamuri, A.Schneyer, and T.B.Thompson (2008).
The Structure of FSTL3{middle dot}Activin A Complex: DIFFERENTIAL BINDING OF N-TERMINAL DOMAINS INFLUENCES FOLLISTATIN-TYPE ANTAGONIST SPECIFICITY.
  J Biol Chem, 283, 32831-32838.
PDB code: 3b4v
18056265 R.V.Korupolu, U.Muenster, J.D.Read, W.Vale, and W.H.Fischer (2008).
Activin A/bone morphogenetic protein (BMP) chimeras exhibit BMP-like activity and antagonize activin and myostatin.
  J Biol Chem, 283, 3782-3790.  
18397882 Y.Makanji, K.L.Walton, M.C.Wilce, K.L.Chan, D.M.Robertson, and C.A.Harrison (2008).
Suppression of inhibin A biological activity by alterations in the binding site for betaglycan.
  J Biol Chem, 283, 16743-16751.  
17295905 D.Weber, A.Kotzsch, J.Nickel, S.Harth, A.Seher, U.Mueller, W.Sebald, and T.D.Mueller (2007).
A silent H-bond can be mutationally activated for high-affinity interaction of BMP-2 and activin type IIB receptor.
  BMC Struct Biol, 7, 6.
PDB codes: 2h62 2h64
17893364 S.Han, P.Loulakis, M.Griffor, and Z.Xie (2007).
Crystal structure of activin receptor type IIB kinase domain from human at 2.0 Angstrom resolution.
  Protein Sci, 16, 2272-2277.
PDB code: 2qlu
17662946 S.Yuzawa, Y.Opatowsky, Z.Zhang, V.Mandiyan, I.Lax, and J.Schlessinger (2007).
Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor.
  Cell, 130, 323-334.
PDB codes: 2e9w 2ec8
17140726 T.F.Lerch, M.Xu, T.S.Jardetzky, K.E.Mayo, I.Radhakrishnan, R.Kazer, L.D.Shea, and T.K.Woodruff (2007).
The structures that underlie normal reproductive function.
  Mol Cell Endocrinol, 267, 1-5.  
17409095 T.F.Lerch, S.Shimasaki, T.K.Woodruff, and T.S.Jardetzky (2007).
Structural and biophysical coupling of heparin and activin binding to follistatin isoform functions.
  J Biol Chem, 282, 15930-15939.
PDB code: 2p6a
16482217 A.E.Harrington, S.A.Morris-Triggs, B.T.Ruotolo, C.V.Robinson, S.Ohnuma, and M.Hyvönen (2006).
Structural basis for the inhibition of activin signalling by follistatin.
  EMBO J, 25, 1035-1045.
PDB codes: 2arp 2arv
16672363 G.P.Allendorph, W.W.Vale, and S.Choe (2006).
Structure of the ternary signaling complex of a TGF-beta superfamily member.
  Proc Natl Acad Sci U S A, 103, 7643-7648.
PDB code: 2goo
16765900 X.Wang, R.H.Baloh, J.Milbrandt, and K.C.Garcia (2006).
Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors.
  Structure, 14, 1083-1092.
PDB codes: 2gh0 2gyr 2gyz
15851468 M.A.Brown, Q.Zhao, K.A.Baker, C.Naik, C.Chen, L.Pukac, M.Singh, T.Tsareva, Y.Parice, A.Mahoney, V.Roschke, I.Sanyal, and S.Choe (2005).
Crystal structure of BMP-9 and functional interactions with pro-region and receptors.
  J Biol Chem, 280, 25111-25118.
PDB code: 1zkz
16252250 R.L.Rich, and D.G.Myszka (2005).
Survey of the year 2004 commercial optical biosensor literature.
  J Mol Recognit, 18, 431-478.  
16186117 R.W.Cook, T.B.Thompson, S.P.Kurup, T.S.Jardetzky, and T.K.Woodruff (2005).
Structural basis for a functional antagonist in the transforming growth factor beta superfamily.
  J Biol Chem, 280, 40177-40186.  
16129674 U.Muenster, C.A.Harrison, C.Donaldson, W.Vale, and W.H.Fischer (2005).
An activin-A/C chimera exhibits activin and myostatin antagonistic properties.
  J Biol Chem, 280, 36626-36632.  
16212511 X.H.Feng, and R.Derynck (2005).
Specificity and versatility in tgf-beta signaling through Smads.
  Annu Rev Cell Dev Biol, 21, 659-693.  
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.