The human cytomegalovirus (HCMV) gene product US11 dislocates MHC I heavy chains from the endoplasmic reticulum (ER) and targets them for proteasomal degradation in the cytosol. To identify the structural and functional domains of US11 that mediate MHC class I molecule degradation, we constructed truncated mutants and chimeric proteins, and analyzed these to determine their intracellular localization and their ability to degrade MHC class I molecules. We found that only the luminal domain of US11 was essential to confer ER localization to the protein but that the ability to degrade MHC class I molecules required both the transmembrane domain and the luminal domain of US11. By analyzing a series of point mutants of the transmembrane domain, we were also able to identify Gln192 and Gly196 as being crucial for the functioning of US11, suggesting that these residues may play a critical role in interacting with the components of the protein degradation machinery.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2005 May 20|
Bibliographical noteFunding Information:
This work was supported by Korean Research Foundation Grant, KRF-2003-015-C00479. Seong-Ok Lee, Eunkyung Kim, and Youngkyun Kim were supported by the BK21 Program of the ministry of Education and Human Resources Development.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology