Functional dissection of HCMV US11 in mediating the degradation of MHC class I molecules.
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 Gln(192) and Gly(196) 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.
Lee
Seong-Ok
SO
Department of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
Hwang
Sujin
S
Park
Junghyun
J
Park
Boyoun
B
Jin
Bong-Suk
BS
Lee
Sungwook
S
Kim
Eunkyung
E
Cho
Sunglim
S
Kim
Youngkyun
Y
Cho
Kwangmin
K
Shin
Jinwook
J
Ahn
Kwangseog
K
D000596:Amino Acids / Q000235:genetics; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017354:Point Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017433:Protein Structure, Secondary; D016601:RNA-Binding Proteins / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology*
D000596:Amino Acids; D015395:Histocompatibility Antigens Class I; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; D014764:Viral Proteins; D046988:Proteasome Endopeptidase Complex