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PMID:12589747

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Citation

Marlow, MS, Brown, CB, Barnett, JV and Krezel, AM (2003) Solution structure of the chick TGFbeta type II receptor ligand-binding domain. J. Mol. Biol. 326:989-97

Abstract

The transforming growth factor beta (TGFbeta) signaling pathway influences cell proliferation, immune responses, and extracellular matrix reorganization throughout the vertebrate life cycle. The signaling cascade is initiated by ligand-binding to its cognate type II receptor. Here, we present the structure of the chick type II TGFbeta receptor determined by solution NMR methods. Distance and angular constraints were derived from 15N and 13C edited NMR experiments. Torsion angle dynamics was used throughout the structure calculations and refinement. The 20 final structures were energy minimized using the generalized Born solvent model. For these 20 structures, the average backbone root-mean-square distance from the average structure is below 0.6A. The overall fold of this 109-residue domain is conserved within the superfamily of these receptors. Chick receptors fully recognize and respond to human TGFbeta ligands despite only 60% identity at the sequence level. Comparison with the human TGFbeta receptor determined by X-ray crystallography reveals different conformations in several regions. Sequence divergence and crystal packing interactions under low pH conditions are likely causes. This solution structure identifies regions were structural changes, however subtle, may occur upon ligand-binding. We also identified two very well conserved molecular surfaces. One was found to bind ligand in the crystallized human TGFbeta3:TGFbeta type II receptor complex. The other, newly identified area can be the interaction site with type I and/or type III receptors of the TGFbeta signaling complex.

Links

PubMed

Keywords

Amino Acid Sequence; Animals; Binding Sites; Chickens; Humans; Ligands; Models, Molecular; Molecular Sequence Data; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Protein Binding; Protein Conformation; Protein-Serine-Threonine Kinases; Receptors, Transforming Growth Factor beta/chemistry; Receptors, Transforming Growth Factor beta/genetics; Receptors, Transforming Growth Factor beta/metabolism; Sequence Alignment; Signal Transduction/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CHICK:TGFR2

located_in

GO:0009897: external side of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

CHICK:TGFR2

located_in

GO:0031012: extracellular matrix

ECO:0000255: match to sequence model evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:TGFR2

part_of

GO:0009897: external side of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

CHICK:TGFR2

involved_in

GO:0051496: positive regulation of stress fiber assembly

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P10600

P

Seeded From UniProt

complete

CHICK:TGFR2

involved_in

GO:1905075: positive regulation of tight junction disassembly

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P10600

P

Seeded From UniProt

complete

CHICK:TGFR2

involved_in

GO:0001666: response to hypoxia

ECO:0000255: match to sequence model evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

involved_in

GO:0007179: transforming growth factor beta receptor signaling pathway

ECO:0000255: match to sequence model evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

involved_in

GO:0010718: positive regulation of epithelial to mesenchymal transition

ECO:0000255: match to sequence model evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

involved_in

GO:0010936: negative regulation of macrophage cytokine production

ECO:0000255: match to sequence model evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

part_of

GO:0031012: extracellular matrix

ECO:0000255: match to sequence model evidence used in manual assertion

C

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

involved_in

GO:0032570: response to progesterone

ECO:0000255: match to sequence model evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

enables

GO:0034714: type III transforming growth factor beta receptor binding

ECO:0000255: match to sequence model evidence used in manual assertion

F

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

involved_in

GO:0045216: cell-cell junction organization

ECO:0000255: match to sequence model evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

enables

GO:0050431: transforming growth factor beta binding

ECO:0000255: match to sequence model evidence used in manual assertion

F

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

involved_in

GO:0050714: positive regulation of protein secretion

ECO:0000255: match to sequence model evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

involved_in

GO:0060325: face morphogenesis

ECO:0000255: match to sequence model evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from

CHICK:TGFR2

involved_in

GO:0070483: detection of hypoxia

ECO:0000255: match to sequence model evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from


See also

References

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