Isolation of recombinant BMP receptor IA ectodomain and its 2:1 complex with BMP‐2

  title={Isolation of recombinant BMP receptor IA ectodomain and its 2:1 complex with BMP‐2},
  author={Thomas A Kirsch and Joachim Nickel and Walter Sebald},
  journal={FEBS Letters},

Crystal structure of the BMP-2–BRIA ectodomain complex

The model reveals the structural basis for discrimination between type I and type II receptors and the variability of receptor–ligand interactions that is seen in BMP–TGF-β systems.

Molecular recognition of BMP-2 and BMP receptor IA

Bone morphogenetic protein-2 (BMP-2) and other members of the TGF-β superfamily regulate the development, maintenance and regeneration of tissues and organs. Binding epitopes for these extracellular

BMP‐2 antagonists emerge from alterations in the low‐affinity binding epitope for receptor BMPR‐II

These findings provide a framework for the molecular description of receptor recognition and activation in the BMP/TGF‐β superfamily.

Type I receptor binding of bone morphogenetic protein 6 is dependent on N‐glycosylation of the ligand

Bone morphogenetic proteins (BMPs), together with transforming growth factor (TGF)‐β and activins/inhibins, constitute the TGF‐β superfamily of ligands, and N‐glycosylation at Asn73 of BMP‐6 in the wrist epitope is crucial for recognition by the activin receptor type I.

The Crystal Structure of the BMP-2: BMPR-IA Complex and the Generation of BMP-2 Antagonists

The identification and characterization of the two receptor binding epitopes in BMP-2 provide new insight into the primary steps of B MP-receptor activation and are transferable to other TGF-&bgr; receptor systems.

BMP-3 and BMP-6 structures illuminate the nature of binding specificity with receptors.

It is illustrated how a single amino acid can regulate the specificity of ligand-receptor binding and potentially alter biological signaling and function in vivo.

A silent H-bond can be mutationally activated for high-affinity interaction of BMP-2 and activin type IIB receptor

The structure-/function studies presented here revealed a new mechanism, in which the energy contribution of a conserved H-bond is modulated by surrounding intramolecular interactions to achieve a switch between low- and high-affinity binding.

A Selection Fit Mechanism in BMP Receptor IA as a Possible Source for BMP Ligand-Receptor Promiscuity

The functional and structural analysis of the BMPR-IA binding antibody AbD1556 mimicking the BMP-2 binding epitope may pave the way for the design of low-molecular weight synthetic receptor binders/inhibitors.



Interaction between Soluble Type I Receptor for Bone Morphogenetic Protein and Bone Morphogenetic Protein-4*

Large-scale expression and purification of extracellular domain of the type I receptor for BMP-2/4 is indicated to be sufficient for high-affinity binding to its ligands and should prove useful in understanding the role of BMP/4 in vivo, because a suitable high-Affinity anti-BMP antibody has yet to be developed.

Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs

Bone morphogenic proteins appear to require the cooperation of these two receptors for optimal binding and for signal transduction, and the combinatorial nature of these receptors and their capacity to crosstalk with the activin receptor system may underlie the multifunctional nature of their ligands.

Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity.

The results identify the basic N-terminal domains of dimeric BMP-2 as heparin-binding sites that are not obligatory for receptor activation but modulate its biological activity.

Crystal structure of human bone morphogenetic protein-2 at 2.7 A resolution.

The crystal structure of human BMP-2 determined by molecular replacement and refined to an R-value of 24.2 % at 2.7 A resolution is reported, showing differences in the flexibility of the N terminus and the orientation of the central alpha-helix as well as two external loops at the fingertips with respect to the scaffold.

Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4.

Results suggest thatALK-3 and ALK-6 are type I receptors for OP-1 and BMP-4; in addition, ALk-2 is a type I receptor shared by activin and OP- 1, but not by B MP-4.

JunB Is Involved in the Inhibition of Myogenic Differentiation by Bone Morphogenetic Protein-2*

JunB is an immediate early gene induced by BMP-2 and transforming growth factor-β and is involved in the early steps of inhibition of myogenic differentiation induced by transforming growth factors family members.

Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects

Results indicate that ActR-II can act as a functional type II receptor for OP-1, as well as for activins, and may have broader effects in vivo than hitherto recognized.

Novel regulators of bone formation: molecular clones and activities.

Human complementary DNA clones corresponding to three polypeptides present in this BMP preparation have been isolated, and expression of the recombinant human proteins have been obtained, and each appears to be independently capable of inducing the formation of cartilage in vivo.

Three-dimensional structure of recombinant human osteogenic protein 1: structural paradigm for the transforming growth factor beta superfamily.

The three-dimensional structure of osteogenic protein 1 (OP-1), a member of the transforming growth factor beta (TGF-beta) superfamily of proteins, is reported to 2.8-A resolution and it is found that although there is limited sequence identity between OP-1 and TGF- beta 2, they share a common polypeptide fold.