Functional dissection of HCMV US11 in mediating the degradation of MHC class I molecules

Seong Ok Lee, Sujin Hwang, Junghyun Park, Boyoun Park, Bong Suk Jin, Sungwook Lee, Eunkyung Kim, Sunglim Cho, Youngkyun Kim, Kwangmin Cho, Jinwook Shin, Kwangseog Ahn

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1262-1267
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume330
Issue number4
DOIs
Publication statusPublished - 2005 May 20

Fingerprint

Dissection
Cytomegalovirus
Endoplasmic Reticulum
Mutant Chimeric Proteins
Degradation
Molecules
Cytosol
Proteolysis
Machinery
Proteins
Genes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, Seong Ok ; Hwang, Sujin ; Park, Junghyun ; Park, Boyoun ; Jin, Bong Suk ; Lee, Sungwook ; Kim, Eunkyung ; Cho, Sunglim ; Kim, Youngkyun ; Cho, Kwangmin ; Shin, Jinwook ; Ahn, Kwangseog. / Functional dissection of HCMV US11 in mediating the degradation of MHC class I molecules. In: Biochemical and Biophysical Research Communications. 2005 ; Vol. 330, No. 4. pp. 1262-1267.
@article{ee4db6a4005347caa34c85195fd37348,
title = "Functional dissection of HCMV US11 in mediating the degradation of MHC class I molecules",
abstract = "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.",
author = "Lee, {Seong Ok} and Sujin Hwang and Junghyun Park and Boyoun Park and Jin, {Bong Suk} and Sungwook Lee and Eunkyung Kim and Sunglim Cho and Youngkyun Kim and Kwangmin Cho and Jinwook Shin and Kwangseog Ahn",
year = "2005",
month = "5",
day = "20",
doi = "10.1016/j.bbrc.2005.03.112",
language = "English",
volume = "330",
pages = "1262--1267",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

Lee, SO, Hwang, S, Park, J, Park, B, Jin, BS, Lee, S, Kim, E, Cho, S, Kim, Y, Cho, K, Shin, J & Ahn, K 2005, 'Functional dissection of HCMV US11 in mediating the degradation of MHC class I molecules', Biochemical and Biophysical Research Communications, vol. 330, no. 4, pp. 1262-1267. https://doi.org/10.1016/j.bbrc.2005.03.112

Functional dissection of HCMV US11 in mediating the degradation of MHC class I molecules. / Lee, Seong Ok; Hwang, Sujin; Park, Junghyun; Park, Boyoun; Jin, Bong Suk; Lee, Sungwook; Kim, Eunkyung; Cho, Sunglim; Kim, Youngkyun; Cho, Kwangmin; Shin, Jinwook; Ahn, Kwangseog.

In: Biochemical and Biophysical Research Communications, Vol. 330, No. 4, 20.05.2005, p. 1262-1267.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Functional dissection of HCMV US11 in mediating the degradation of MHC class I molecules

AU - Lee, Seong Ok

AU - Hwang, Sujin

AU - Park, Junghyun

AU - Park, Boyoun

AU - Jin, Bong Suk

AU - Lee, Sungwook

AU - Kim, Eunkyung

AU - Cho, Sunglim

AU - Kim, Youngkyun

AU - Cho, Kwangmin

AU - Shin, Jinwook

AU - Ahn, Kwangseog

PY - 2005/5/20

Y1 - 2005/5/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=20144387915&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20144387915&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2005.03.112

DO - 10.1016/j.bbrc.2005.03.112

M3 - Article

VL - 330

SP - 1262

EP - 1267

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -