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Publication Abstract from PubMed

Transforming growth factor beta is a disulfide-linked dimeric cytokine that occurs in three highly related isoforms (TGFbeta1-TGFbeta3) engaged in signaling functions through binding of cognate TGFbeta receptors. To regulate this pathway, the cytokines are biosynthesized as inactive pro-TGFbetas with an N-terminal latency-associated protein preceding the mature moieties. Due to their pleiotropic implications in physiology and pathology, TGFbetas are privileged objects of in vitro studies. However, such studies have long been limited by the lack of efficient human recombinant expression systems of native, glycosylated, and homogenous proteins. Here, we developed pro-TGFbeta2 production systems based on human Expi293F cells, which yielded >2 mg of pure histidine- or Strep-tagged protein per liter of cell culture. We assayed this material biophysically and in crystallization assays and obtained a different crystal form of mature TGFbeta2, which adopted a conformation deviating from previous structures, with a distinct dimeric conformation that would require significant rearrangement for binding of TGFbeta receptors. This new conformation may be reversibly adopted by a certain fraction of the mature TGbeta2 population and represent a hitherto undescribed additional level of activity regulation of the mature growth factor once the latency-associated protein has been separated.

Recombinant production, purification, crystallization, and structure analysis of human transforming growth factor beta2 in a new conformation.,Del Amo-Maestro L, Marino-Puertas L, Goulas T, Gomis-Ruth FX Sci Rep. 2019 Jun 17;9(1):8660. doi: 10.1038/s41598-019-44943-4. PMID:31209258^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.