Order and disorder-An integrative structure of the full-length human growth hormone receptor.

Because of its small size (70 kilodalton) and large content of structural disorder (>50%), the human growth hormone receptor (hGHR) falls between the cracks of conventional high-resolution structural biology methods. Here, we study the structure of the full-length hGHR in nanodiscs with small-angle x-ray scattering (SAXS) as the foundation. We develop an approach that combines SAXS, x-ray diffraction, and NMR spectroscopy data obtained on individual domains and integrate these through molecular dynamics simulations to interpret SAXS data on the full-length hGHR in nanodiscs.

A growth hormone receptor SNP promotes lung cancer by impairment of SOCS2-mediated degradation.

Both humans and mice lacking functional growth hormone (GH) receptors are known to be resistant to cancer. Further, autocrine GH has been reported to act as a cancer promoter. Here we present the first example of a variant of the GH receptor (GHR) associated with cancer promotion, in this case lung cancer.

Single methyl groups can act as toggle switches to specify transmembrane Protein-protein interactions.

Transmembrane domains (TMDs) engage in protein-protein interactions that regulate many cellular processes, but the rules governing the specificity of these interactions are poorly understood. To discover these principles, we analyzed 26-residue model transmembrane proteins consisting exclusively of leucine and isoleucine (called LIL traptamers) that specifically activate the erythropoietin receptor (EPOR) in mouse cells to confer growth factor independence. We discovered that the placement of a single side chain methyl group at specific positions in a traptamer determined whether it associated productively with the TMD of the human EPOR, the mouse EPOR, or both receptors.

Light-Induced Rearrangement of the β5 Strand in the BLUF Photoreceptor SyPixD (Slr1694).

The structural changes that facilitate signal transduction in blue light sensors using FAD (BLUF) photoreceptors and confer the stability of the rearranged hydrogen bond network between flavin and protein in the signaling state are still poorly understood. Here, we investigate a semiconserved Trp residue in SyPixD (Slr1694) by isotope-edited vibrational spectroscopy and site-directed mutagenesis. In the signaling state, a β-sheet structure involving the backbone of W91 is formed without apparent change of environment of the W91 indole side chain.

Exploiting hydrophobicity for efficient production of transmembrane helices for structure determination by NMR spectroscopy.

Despite the biological and pharmaceutical significance of membrane proteins, their tertiary structures constitute less than 3% of known structures. One of the major obstacles for initiating structural studies of membrane proteins by NMR spectroscopy is the generation of high amounts of isotope-labeled protein. In this work, we have exploited the hydrophobic nature of membrane proteins to develop a simple and efficient production scheme for isotope-labeled single-pass transmembrane domains (TMDs) with or without intrinsically disordered regions.