Wohl, Alexander P., Troilo, Helen ORCID: 0000-0003-0537-1786, Collins, Richard F., Baldock, Clair ORCID: 0000-0003-3497-1959 and Sengle, Gerhard (2016). Extracellular Regulation of Bone Morphogenetic Protein Activity by the Microfibril Component Fibrillin-1. J. Biol. Chem., 291 (24). S. 12732 - 12747. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X
Full text not available from this repository.Abstract
Since the discovery of bone morphogenetic proteins (BMPs) as pluripotent cytokines extractable from bone matrix, it has been speculated how targeting of BMPs to the extracellular matrix (ECM) modulates their bioavailability. Understanding these processes is crucial for elucidating pathomechanisms of connective tissue disorders characterized by ECM deficiency and growth factor dysregulation. Here, we provide evidence for a new BMP targeting and sequestration mechanism that is controlled by the ECM molecule fibrillin-1. We present the nanoscale structure of the BMP-7 prodomain-growth factor complex using electron microscopy, small angle x-ray scattering, and circular dichroism spectroscopy, showing that it assumes an open V-like structure when it is bioactive. However, upon binding to fibrillin-1, the BMP-7 complex is rendered into a closed ring shape, which also confers latency to the growth factor, as demonstrated by bioactivity measurements. BMP-7 prodomain variants were used to map the critical epitopes for prodomain-growth factor and prodomain-prodomain binding. Together, these data show that upon prodomain binding to fibrillin-1, the BMP-7 complex undergoes a conformational change, which denies access of BMP receptors to the growth factor.
Item Type: | Journal Article | ||||||||||||||||||||||||
Creators: |
|
||||||||||||||||||||||||
URN: | urn:nbn:de:hbz:38-272372 | ||||||||||||||||||||||||
DOI: | 10.1074/jbc.M115.704734 | ||||||||||||||||||||||||
Journal or Publication Title: | J. Biol. Chem. | ||||||||||||||||||||||||
Volume: | 291 | ||||||||||||||||||||||||
Number: | 24 | ||||||||||||||||||||||||
Page Range: | S. 12732 - 12747 | ||||||||||||||||||||||||
Date: | 2016 | ||||||||||||||||||||||||
Publisher: | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | ||||||||||||||||||||||||
Place of Publication: | BETHESDA | ||||||||||||||||||||||||
ISSN: | 1083-351X | ||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||
Uncontrolled Keywords: |
|
||||||||||||||||||||||||
Refereed: | Yes | ||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/27237 |
Downloads
Downloads per month over past year
Altmetric
Export
Actions (login required)
View Item |