First Author | Becker V | Year | 2008 |
Journal | Biochemistry | Volume | 47 |
Issue | 45 | Pages | 11771-82 |
PubMed ID | 18855427 | Mgi Jnum | J:143279 |
Mgi Id | MGI:3826315 | Doi | 10.1021/bi801425e |
Citation | Becker V, et al. (2008) Packing density of the erythropoietin receptor transmembrane domain correlates with amplification of biological responses. Biochemistry 47(45):11771-82 |
abstractText | The formation of signal-promoting dimeric or oligomeric receptor complexes at the cell surface is modulated by self-interaction of their transmembrane (TM) domains. To address the importance of TM domain packing density for receptor functionality, we examined a set of asparagine mutants in the TM domain of the erythropoietin receptor (EpoR). We identified EpoR-T242N as a receptor variant that is present at the cell surface similar to wild-type EpoR but lacks visible localization in vesicle-like structures and is impaired in efficient activation of specific signaling cascades. Analysis by a molecular modeling approach indicated an increased interhelical distance for the EpoR-T242N TM dimer. By employing the model, we designed additional mutants with increased or decreased packing volume and confirmed a correlation between packing volume and biological responsiveness. These results propose that the packing density of the TM domain provides a novel layer for fine-tuned regulation of signal transduction and cellular decisions. |