title: Biological and physicochemical evaluation of the conformational stability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
abstract: Tumor necrosis factor (TNF)-related, apoptosis-inducing ligand (Apo2L/TRAIL) has a unique homotrimeric structure, and its conformational stability is essential for its apoptotic activity. The conformational stability of a modified version of TRAIL(114-281) with two additional domains of histidine tag and isoleucine zipper [His-ILZ-TRAIL(114-281)] was evaluated in various pH environments according to three different biological or physicochemical considerations: cytotoxicity, antibody-binding affinity, and tertiary structure. The biological properties of His-ILZ-TRAIL(114-281) were the most stably maintained at pH 6.0. The physicochemical analyses (circular dichroism and fluorescence spectroscopy) demonstrate that its bioactivity loss by pH challenge was originated from its structural collapse as a homotrimer.
authors.affiliation: Drug Targeting Laboratory, College of Pharmacy, SungKyunKwan University, 300 Chonchon-dong, Jangan-ku, Suwon City, 440-746, Korea.
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Shin
authors.forename: Su Young
authors.initials: SY
authors.lastname: Chae
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Jin
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
mesh_terms: D000915:Antibody Affinity / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011487:Protein Conformation / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry* / Q000494:pharmacology; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand