Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4

Chih Chin Huang; Son N. Lam; Priyamvada Acharya; Min Tang; Shi Hua Xiang; Syed Shahzad-Ul-Hussan; Robyn L. Stanfield; James Robinson; Joseph Sodroski; Ian A. Wilson; Richard Wyatt; Carole A. Bewley; Peter D. Kwong

doi:10.1126/science.1145373

Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4

Chih Chin Huang, Son N. Lam, Priyamvada Acharya, Min Tang, Shi Hua Xiang, Syed Shahzad-Ul-Hussan, Robyn L. Stanfield, James Robinson, Joseph Sodroski, Ian A. Wilson, Richard Wyatt, Carole A. Bewley, Peter D. Kwong

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Abstract

The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (α-helix) and 412d (extendedloop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system.

Original language	English (US)
Pages (from-to)	1930-1934
Number of pages	5
Journal	Science
Volume	317
Issue number	5846
DOIs	https://doi.org/10.1126/science.1145373
State	Published - Sep 28 2007
Externally published	Yes

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title = "Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4",

abstract = "The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (α-helix) and 412d (extendedloop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system.",

author = "Huang, {Chih Chin} and Lam, {Son N.} and Priyamvada Acharya and Min Tang and Xiang, {Shi Hua} and Syed Shahzad-Ul-Hussan and Stanfield, {Robyn L.} and James Robinson and Joseph Sodroski and Wilson, {Ian A.} and Richard Wyatt and Bewley, {Carole A.} and Kwong, {Peter D.}",

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language = "English (US)",

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T1 - Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4

AU - Huang, Chih Chin

AU - Lam, Son N.

AU - Acharya, Priyamvada

AU - Tang, Min

AU - Xiang, Shi Hua

AU - Shahzad-Ul-Hussan, Syed

AU - Stanfield, Robyn L.

AU - Robinson, James

AU - Sodroski, Joseph

AU - Wilson, Ian A.

AU - Wyatt, Richard

AU - Bewley, Carole A.

AU - Kwong, Peter D.

PY - 2007/9/28

Y1 - 2007/9/28

N2 - The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (α-helix) and 412d (extendedloop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system.

AB - The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (α-helix) and 412d (extendedloop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system.

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Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4

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