Month: April 2017

Development of a multipurpose scaffold for the display of peptide loops

Maxim Rossmann, Sandra J. Greive, Tommaso Moschetti, Michael Dinan, Marko Hyvönen

Protein Engineering, Design and Selection 30: 419–430 (2017)
DOI: 10.1093/protein/gzx017
Pubmed: 228444399


Protein-protein interactions (PPIs) determine a wide range of biological processes and analysis of these dynamic networks is increasingly becoming a mandatory tool for studying protein function. Using the globular ATPase domain of recombinase RadA as a scaffold, we have developed a peptide display system (RAD display), which allows for the presentation of target peptides, protein domains or full-length proteins and their rapid recombinant production in bacteria. Continue reading →

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Structure and activation of pro-activin A

Xuelu Wang, Gerhard Fischer and Marko Hyvönen

Nature Communications 7:1205, 2016
DOI: 10.1038/ncomms12052
Pubmed: 27373274

PDB coordinates: 5HLY (3D view), 5HLZ (3D view)


Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein.

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