The N-terminal SRCR-SID domain of gp-340 interacts with HIV type 1 gp120 sequences and inhibits viral infection.
Proteins encoded by the SRCR superfamily including gp340 recognize repeated patterns on pathogenic microorganisms and play important roles in innate immune defense as well as epithelial cell differentiation. Based upon the presence of SRCR domains in proteins with broad binding specificities and high amino acid sequence homology, it was speculated that SRCR domains may be involved in ligand binding. In this study, a truncated gp340 molecule representing the N-terminal sequence including the first SRCR and one-half of the first SID was expressed in mammalian 293 cells as a 35-kDa recombinant protein. The expressed protein was recognized by a panel of antibodies specific for human salivary agglutinin (SAG) and the full-length parental gp340 and exhibited biological properties similar to the entire 340-kDa glycoprotein. The truncated gp340 protein bound to the same HIV-1 V3 sequences previously identified to interact with full-length SAG in a Ca2+ -dependent manner. The recombinant N-terminal SRCR protein also demonstrated potent anti-HIV- 1 activity against both CCR5- and CXCR4-using isolates, similar to the full-length glycoprotein. We have, thus, demonstrated that the N-terminal SRCR of gp340 directly interacts with viral gp120 and likely mediates anti-HIV-1 activity via this interaction.
Wu
Zhiwei
Z
Department of Biochemistry, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania 19104, USA.
Lee
Sang
S
Abrams
William
W
Weissman
Drew
D
Malamud
Daniel
D
D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002135:Calcium-Binding Proteins; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D019380:Anti-HIV Agents; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D015699:HIV Envelope Protein gp120; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; C116303:glycoprotein 340