@article{fdi:010042974,
  title = {{H}ighly conserved beta 16/beta 17 beta-hairpin structure in human immunodeficiency virus type 1 {YU}2 gp120 is critical for {CCR}5 binding},
  author = {{M}echulam, {A}. and {C}erutti, {M}. and {P}ugniere, {M}. and {M}iss{\'e}, {D}oroth{\'e}e and {G}ajardo, {J}. and {R}oquet, {F}. and {R}obinson, {J}. and {V}eas, {F}rancisco},
  editor = {},
  language = {{ENG}},
  abstract = {{W}hereas gp120 {CD}4-induced structures have been largely documented and at least in part elucidated by crystallization, information about gp120 coreceptor-induced structures remains incomplete despite numerous studies. {I}n this work, mutations were carried out in a selected internal region of {HIV}-1/{YU}2 gp120, proximal to the {CD}4-binding site, because of its highly conserved nature among retroviruses and its high structural stability. {T}he targeted residues, belonging to the beta 16/beta 17 beta-hairpin, modulate gp120 binding to {CD}4 and gp120-{CD}4 complex binding to {CCR}5. {T}hus, it appears that this gp120 structure acts as a hinge between the {CD}4-binding site and the putative coreceptor binding structure. {S}ubstitution of amino acid residues like {E}381{A} did not affect gp120 binding to {CD}4 and did not induce significant structural changes in gp120, as demonstrated by epitope analysis, {BIACORE} analysis, and circular dichroism. {N}evertheless, {E}381 has a critical influence on the maintenance of {CCR}5 coreceptor binding by forming a salt bridge with {K}207. {A}nother important element of the beta-hairpin in this interaction is the probable hydrophobic link between {F}383 and {I}420. {A}ltogether, these results suggest that the beta-hairpin structure likely governs interactions between the surface of gp120 with native {CCR}5 or the {CCR}5 amino-terminal domain ({CCR}5-{N}t). {T}he mutations within the beta-hairpin had a direct effect on the proximal surface of the bridging sheet, the putative {CCR}5 surface, and the gp120 {YU}2 {HIV}-1-{CD}4 binding site. {T}hese results on the gp120-{CCR}5-{N}t binding mechanism contribute to our understanding of {CCR}5 and {HIV}-1 gp120 association and {HIV}-1 entry; they may also contribute to designing novel inhibitors.},
  keywords = {{HIV} 1 ; gp120 structure ; gp120 receptor binding ; {CD}4 ; {CCR}5},
  booktitle = {},
  journal = {{J}ournal of {M}olecular {M}edicine},
  volume = {83},
  numero = {7},
  pages = {542--552},
  ISSN = {0946-2716},
  year = {2005},
  DOI = {10.1007/s00109-005-0673-1},
  URL = {https://www.documentation.ird.fr/hor/fdi:010042974},
}