Association of human tumor necrosis factor-related apoptosis inducing ligand with membrane upon acidification
SCIE
SCOPUS
- Title
- Association of human tumor necrosis factor-related apoptosis inducing ligand with membrane upon acidification
- Authors
- Nam, GH; Choi, KY
- Date Issued
- 2002-11
- Publisher
- BLACKWELL PUBLISHING LTD
- Abstract
- 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 he proteins of TNF family. Recently, he crystal structure of human TRAIL showed that TRAIL is a homotrimeric protein whose subunits contain mainly beta-sheets. We characterized the structural changes of recombinan human TRAIL induced by acidification and the biological implication of he structural characteristics a acidic pH in the interaction with the lipid bilayer. A acidic pH below pH 4.5, TRAIL resulted in substantial structural changes to a molten globule (MG)-like state. Far-UV CD spectrum of TRAIL indicated hat he acidification induced a helices that are absent in he native state. TRAIL a acidic pH exhibited significant change of tertiary structures as reflected in the near-UV CD spectrum. Thermal transition curve indicated hat here was less cooperation at acidic pH than at neutral pH in he thermal denaturation of TRAIL. Moreover, TRAIL at the MG-like state not only enhanced the binding ability to liposomes, but also increased he release rate of a fluorescent dye, calcein, encapsulated in liposomes. The binding assay with anilinonaphthalene-8-sulfonic acid revealed hat he surface hydrophobicity of TRAIL was increased while tryptophan residues became more exposed to solvent as judged by blue shift of he maximum fluorescence wavelength. Taken together, our results demonstrate hat he acidification of human TRAIL induces the MG-like state in vitro and makes he membrane permeable through the favorable interaction of TRAIL with the membrane, implicating hat general intrinsic properties such as TRAIL, TNF-alpha and lymphotoxin are shared by TNF family members.
- Keywords
- TNF-related apoptosis inducing ligand; TNF family; acidication; molten globule (MG)-like state; alpha-helices; FACTOR-ALPHA; CRYSTAL-STRUCTURE; COLICIN-A; PHOSPHOLIPID MEMBRANES; TUMORICIDAL ACTIVITY; MOLTEN-GLOBULE; HUMAN TRAIL; LOW PH; RESOLUTION; INSERTION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/18858
- DOI
- 10.1046/J.1432-1033.
- ISSN
- 0014-2956
- Article Type
- Article
- Citation
- EUROPEAN JOURNAL OF BIOCHEMISTRY, vol. 269, no. 21, page. 5280 - 5287, 2002-11
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