Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120.
The conserved surface of the HIV-1 gp120 envelope glycoprotein that binds to the HIV-1 coreceptor is protected from humoral recognition by multiple layers of camouflage. Here we present sequence and genomic analyses for 12 antibodies that pierce these defenses and determine the crystal structures of 5. The data reveal mechanisms and atomic-level details for three unusual immune features: posttranslational mimicry of coreceptor by tyrosine sulfation of antibody, an alternative molecular mechanism controlling such sulfation, and highly selective V(H)-gene usage. When confronted by extraordinary viral defenses, the immune system unveils novel adaptive capabilities, with tyrosine sulfation enhancing the vocabulary of antigen recognition.
Huang
Chih-chin
CC
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Venturi
Miro
M
Majeed
Shahzad
S
Moore
Michael J
MJ
Phogat
Sanjay
S
Zhang
Mei-Yun
MY
Dimitrov
Dimiter S
DS
Hendrickson
Wayne A
WA
Robinson
James
J
Sodroski
Joseph
J
Wyatt
Richard
R
Choe
Hyeryun
H
Farzan
Michael
M
Kwong
Peter D
PD
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000595:Amino Acid Sequence; D000917:Antibody Formation; D015704:CD4 Antigens / Q000276:immunology; D018360:Crystallography, X-Ray; D005803:Genes, Immunoglobulin; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D013431:Sulfates / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D013431:Sulfates; C005662:tyrosine O-sulfate; D014443:Tyrosine