The role of post-translational modifications of the CXCR4 amino terminus in stromal-derived factor 1 alpha association and HIV-1 entry.
The chemokine receptor CXCR4 plays critical roles in development, immune function, and human immunodeficiency virus type 1 (HIV-1) entry. Here we demonstrate that, like the CC-chemokine receptors CCR5 and CCR2b, CXCR4 is posttranslationally modified by sulfation of its amino-terminal tyrosines. The sulfate group at tyrosine 21 contributes substantially to the ability of CXCR4 to bind its ligand, stromal derived factor 1 alpha. Tyrosine sulfation plays a less significant role in CXCR4-dependent HIV-1 entry than in CCR5-dependent HIV-1 entry. In some cell lines, CXCR4 is efficiently modified by a chondroitin sulfate chain at serine 18, but neither HIV-1 entry nor stromal derived factor 1 alpha binding was affected by loss of this glycosaminoglycan. These data demonstrate a functional role for tyrosine sulfate in the CXC-chemokine receptor family and underscore a general difference in HIV-1 utilization of CCR5 and CXCR4.
Farzan
Michael
M
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Babcock
Gregory J
GJ
Vasilieva
Natalya
N
Wright
Paulette L
PL
Kiprilov
Enko
E
Mirzabekov
Tajib
T
Choe
Hyeryun
H
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D002809:Chondroitin Sulfates / Q000378:metabolism; D004285:Dogs; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D019718:Receptors, CXCR4 / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; C005662:tyrosine O-sulfate; D014443:Tyrosine; D012694:Serine; D002809:Chondroitin Sulfates