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PDBsum entry 2hlq
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References listed in PDB file
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Key reference
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Title
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High resolution structures of the bone morphogenetic protein type ii receptor in two crystal forms: implications for ligand binding.
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Authors
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P.D.Mace,
J.F.Cutfield,
S.M.Cutfield.
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Ref.
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Biochem Biophys Res Commun, 2006,
351,
831-838.
[DOI no: ]
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PubMed id
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Abstract
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BMPRII is a type II TGF-beta serine threonine kinase receptor which is integral
to the bone morphogenetic protein (BMP) signalling pathway. It is known to bind
BMP and growth differentiation factor (GDF) ligands, and has overlapping ligand
specificity with the activin type II receptor, ActRII. In contrast to activin
and TGF-beta type ligands, BMPs bind to type II receptors with lower affinity
than type I receptors. Crystals of the BMPRII ectodomain were grown in two
different forms, both of which diffracted to high resolution. The tetragonal
form exhibited some disorder, whereas the entire polypeptide was seen in the
orthorhombic form. The two structures retain the basic three-finger toxin fold
of other TGF-beta receptor ectodomains, and share the main hydrophobic patch
used by ActRII to bind various ligands. However, they present different
conformations of the A-loop at the periphery of the proposed ligand-binding
interface, in conjunction with rearrangement of a disulfide bridge within the
loop. This particular disulfide (Cys94-Cys117) is only present in BMPRII and
activin receptors, suggesting that it is important for their likely shared mode
of binding. Evidence is presented that the two crystal forms represent
ligand-bound and free conformations of BMPRII. Comparison with the solved
structure of ActRII bound to BMP2 suggests that His87, unique amongst TGF-beta
receptors, may play a key role in ligand recognition.
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