The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Baldwin, R. L.
Right arrow Articles by Wisnieski, B. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baldwin, R. L.
Right arrow Articles by Wisnieski, B. J.

The Journal of Immunology, Vol 154, Issue 2 790-798, Copyright © 1995 by American Association of Immunologists

ARTICLES

Conformation and ion channel activity of lymphotoxin at neutral and low pH

RL Baldwin, T Mirzabekov, BL Kagan and BJ Wisnieski
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024.

Lymphotoxin (LT or TNF-beta), a T cell-derived lymphokine with partial homology to TNF-alpha, was found to bind to dimyristoylphosphatidylcholine vesicles in a pH-dependent manner: binding increased with decreasing pH. Binding was not limited to surface association with phospholipid head groups because studies with a photoreactive membrane-restricted probe revealed protein penetration of the hydrocarbon core of the bilayer. Intramembranous photolabeling of the trimeric form of LT demonstrated maintenance of quaternary structure upon bilayer insertion. The efficiency of insertion was greatly enhanced with gel-phase bilayers compared with fluid phase bilayers even though the binding efficiency was much lower. Hence, binding and insertion represent two distinct physical processes. Intrinsic fluorescence and dye binding assays showed that the acid- facilitated membrane interactions stemmed from acid-induced changes in protein conformation. The acquisition of hydrophobic characteristics through these conformational changes supplies a physical explanation for LT conversion from a water-soluble form to a membrane-embedded structure. Moreover, the use of vesicle-embedded LT to prepare planar bilayers vs the addition of soluble LT subsequent to bilayer formation demonstrated that LT exhibits channel activity and that low pH-induced membrane insertion precedes and is distinct from expression of voltage- dependent ion gating. LT's ability to associate intimately with lipid vesicles and form ion channels mirrors the behavior of TNF-alpha. Thus, although LT and TNF-alpha are secreted by different cell types, the conservation of membrane binding, insertion, and channel-forming activities suggests a functional role in response induction.


This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
N. Fukuda, C. Jayr, A. Lazrak, Y. Wang, R. Lucas, S. Matalon, and M. A. Matthay
Mechanisms of TNF-{alpha} stimulation of amiloride-sensitive sodium transport across alveolar epithelium
Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1258 - L1265.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S.-S. Cha, J.-S. Kim, H.-S. Cho, N.-K. Shin, W. Jeong, H.-C. Shin, Y. J. Kim, J. H. Hahn, and B.-H. Oh
High Resolution Crystal Structure of a Human Tumor Necrosis Factor-alpha Mutant with Low Systemic Toxicity
J. Biol. Chem., January 23, 1998; 273(4): 2153 - 2160.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1995 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1995 by The American Association of Immunologists, Inc. All rights reserved.