An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: Relationship to cystatins and the tumor suppressor TIG1

Aagaard, A., Listwan, P., Cowieson, N. P., Huber, T. L., Ravasi, T., Wells, C. A., Flanagan, J. U., Kellie, S., Hume, D. A., Kobe, B. and Martin, J. L. (2005) An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: Relationship to cystatins and the tumor suppressor TIG1. Structure, 13 2: 309-317. doi:10.1016/j.str.2004.12.013


Author Aagaard, A.
Listwan, P.
Cowieson, N. P.
Huber, T. L.
Ravasi, T.
Wells, C. A.
Flanagan, J. U.
Kellie, S.
Hume, D. A.
Kobe, B.
Martin, J. L.
Title An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: Relationship to cystatins and the tumor suppressor TIG1
Journal name Structure   Check publisher's open access policy
ISSN 0969-2126
Publication date 2005-01-01
Sub-type Article (original research)
DOI 10.1016/j.str.2004.12.013
Volume 13
Issue 2
Start page 309
End page 317
Total pages 9
Place of publication Cambridge
Publisher Cell Press
Collection year 2005
Language eng
Subject C1
270199 Biochemistry and Cell Biology not elsewhere classified
780105 Biological sciences
Abstract Latexin, the only known mammalian carboxypeptidase inhibitor, has no detectable sequence similarity with plant and parasite inhibitors, but it is related to a human putative tumor suppressor protein, TIG1. Latexin is expressed in the developing brain, and we find that it plays a role in inflammation, as it is expressed at high levels and is inducible in macrophages in concert with other protease inhibitors and potential protease targets. The crystal structure of mouse latexin, solved at 1.83 Angstrom resolution, shows no structural relationship with other carboxypeptidase inhibitors. Furthermore, despite a lack of detectable sequence duplication, the structure incorporates two topologically analogous domains related by pseudo two-fold symmetry. Surprisingly, these domains share a cystatin fold architecture found in proteins that inhibit cysteine proteases, suggesting an evolutionary and possibly functional relationship. The structure of the tumor suppressor protein TIG1 was modeled, revealing its putative membrane binding surface.
Keyword Biophysics
Cell Biology
Electron-density Maps
Ray Crystal-structure
Induced Gene-1 Tig1
Angstrom Resolution
Binding-sites
Mast-cells
Protein
Expression
Macrophages
Program
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 16:23:02 EST