6i9j
Human transforming growth factor beta2 in a tetragonal crystal form
Structural highlights
DiseaseTGFB2_HUMAN Note=A chromosomal aberration involving TGFB2 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with HDAC9. Defects in TGFB2 are the cause of Loeys-Dietz syndrome 4 (LDS4) [MIM:614816. An aortic aneurysm syndrome with widespread systemic involvement. LDS4 is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm and subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity, bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities, dural ectasia, joint hyperflexibility, and thin skin with easy bruising and striae.[1] FunctionTGFB2_HUMAN TGF-beta 2 has suppressive effects on interleukin-2 dependent T-cell growth. Publication Abstract from PubMedTransforming 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. References
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