The SNP rs4252548 (R112H) which is associated with reduced human height compromises the stability of IL-11

In this study, we show by molecular replacement that Arg-112 does not participate in binding of IL-11 to its receptors IL-11R and glycoprotein 130 (gp130). Recombinant IL-11 R112H expressed in E. coli displays a correct four-helix-bundle folding topology, and binds with similar affinity to IL-11R and the IL-11/IL-11R/gp130 complex. IL-11 R112H induces cell proliferation and phosphorylation of the downstream transcription factor STAT3 indistinguishable from IL-11. However, IL-11 R112H fails to support the survival of osteoclast progenitor cells and is less thermally stable, which is caused by the loss of the positive charge on the protein surface since protonation of the histidine side chain recovers stability.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research