TAILIEUCHUNG - Báo cáo Y học: Association of human tumor necrosis factor-related apoptosis inducing ligand with membrane upon acidification

Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) has been known to induce tumor-specific apoptosis and to share the structural and functional char-acteristics with the proteins of TNF family. Recently, the crystal structure of humanTRAIL showed that TRAIL is a homotrimeric protein whose subunits contain mainly b-sheets. We characterized the structural changes of recombinant human TRAIL induced byacidification and the biological implication of the structural characteristics at acidic pH in the interaction with the lipid bilayer. . | Eur. J. Biochem. 269 5280-5287 2002 FEBS 2002 doi Association of human tumor necrosis factor-related apoptosis inducing ligand with membrane upon acidification Gyu Hyun Nam and Kwan Yong Choi National Research Laboratory of Protein Folding and Engineering Division of Molecular and Life Sciences Pohang University of Science and Technology Pohang Republic of Korea Tumor necrosis factor TNF -related apoptosis inducing ligand TRAIL has been known to induce tumor-specific apoptosis and to share the structural and functional characteristics with the proteins of TNF family. Recently the crystal structure of human TRAIL showed that TRAIL is a homotrimeric protein whose subunits contain mainly b-sheets. We characterized the structural changes of recombinant human TRAIL induced byacidification and the biological implication of the structural characteristics at acidic pH in the interaction with the lipid bilayer. At acidic pH below pH TRAIL resulted in substantial structural changes to a molten globule MG -like state. Far-UV CD spectrum of TRAIL indicated that the acidification induced a-helices that are absent in the native state. TRAIL at acidic pH exhibited significant change of tertiary structures as reflected in the near-UV CD spectrum. Thermal transition curve indicated that there was less cooperation at acidic pH than at neutral pH in the thermal denaturation of TRAIL. Moreover TRAIL at the MG-like state not onlyenhanced the binding abilityto liposomes but also increased the release rate of a fluorescent dye calcein encapsulated in liposomes. The binding assay with anninoniihhtaalene-8-sulfonic acid revealed that the surface hydrophobicity of TRAIL was increased while tryptophan residues became more exposed to solvent as judged by bhee hhift ơi hie maximum fluorescence wavelength. Taken together our results demonstrate that the acidification of human TRAIL induces the MG-like state in vitro and makes the membrane permeable through .

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