The binding of HIV-1 gp41 membrane proximal domain to its mucosal receptor, galactosyl ceramide, is structure-dependent.

The binding of HIV-1 gp41 membrane proximal domain to its mucosal receptor, galactosyl ceramide, is structure-dependent. Research Abstract Details 

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The binding of HIV-1 gp41 membrane proximal domain to its mucosal receptor, galactosyl ceramide, is structure-dependent. Abstract Text:

Huifeng Yu,Annette Alfsen,Daniela Tudor,Morgane Bomsel,

The peptide of HIV-1 envelope gp41 (a.a 628-683), referred to herein as P5, contains P1, a conserved galactose-specific lectin domain for binding the mucosal HIV-1-receptor, galactosyl ceramide (GalCer), as shown earlier, and a potential calcium-binding site (a.a 628-648). P1 contains contiguous epitopes recognized by the broadly neutralizing antibodies 2F5, 4E10, Z13. However, similar neutralizing antibodies could not be raised in animal model using immunogens based on these epitopes. We now show that the structure of both P5 and P1 peptides, as measured by circular dichroism, differs according to their environment: aqueous or lipidic, and as a function of calcium concentration. P5, but not P1, binds to calcium with a low binding affinity constant in the order of 2.5x10(4). Calcium binding results in a conformational change of P5, leading in turn to a decrease in affinity for GalCer. Hence, the affinity of the gp41-lectin site for the galactose harbored by the mucosal HIV-1 receptor GalCer is modulated by the peptide secondary and tertiary structure and the local environment. Therefore, definition of the conformation of this novel extended gp41 membrane proximal region, containing the conserved peptide P1 and the Ca(2+) binding site, could help designing an immunogen efficient at inducing neutralizing anti-HIV-1 antibodies.

The binding of HIV-1 gp41 membrane proximal domain to its mucosal receptor, galactosyl ceramide, is structure-dependent. Publishing Authors By Initials

H Yu,A Alfsen,D Tudor,M Bomsel,

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The binding of HIV-1 gp41 membrane proximal domain to its mucosal receptor, galactosyl ceramide, is structure-dependent. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cell calcium

VOLUME: 43

Page Numbers: 73-82

Journal Abbreviation: Cell Calcium

ISSN: 0143-4160

DAY: 5

MONTH: 06

YEAR: 2007

The binding of HIV-1 gp41 membrane proximal domain to its mucosal receptor, galactosyl ceramide, is structure-dependent. Information

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LANGUAGE: eng

NlmUniqueID: 8006226

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AFFILIATION: Entrée Muqueuse du VIH et Immunité Muqueuse, Département de Biologie Cellulaire, Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), 22 rue Méchain, 75014 Paris, France; Inserm, U567 Paris, France.

Country: Scotland

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MEDLINETA: Cell Calcium

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