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PMID: 17363299 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Structures of T Cell immunoglobulin mucin receptors 1 and 2 reveal mechanisms for regulation of immune responses by the TIM receptor family.

Immunity ·Vol. 26 ·No. 3 ·2007-03-00 ·Pages 299-310

Santiago C, Ballesteros A, Tami C, Martínez-Muñoz L, Kaplan GG, Casasnovas JM

Abstract

The T cell immunoglobulin mucin (TIM) receptors are involved in the regulation of immune responses, autoimmunity, and allergy. Structures of the N-terminal ligand binding domain of the murine mTIM-1 and mTIM-2 receptors revealed an immunoglobulin (Ig) fold, with four Cys residues bridging a distinctive CC' loop to the GFC beta-sheet. The structures showed two ligand-recognition modes in the TIM family. The mTIM-1 structure identified a homophilic TIM-TIM adhesion interaction, whereas the mTIM-2 domain formed a dimer that prevented homophilic binding. Biochemical, mutational, and cell adhesion analyses confirmed the divergent ligand-binding modes revealed by the structures. Structural features characteristic of mTIM-1 appear conserved in human TIM-1, which also mediated homophilic interactions. The extracellular mucin domain enhanced binding through the Ig domain, modulating TIM receptor functions. These results explain the divergent immune functions described for the murine receptors and the role of TIM-1 as a cell adhesion receptor in renal regeneration and cancer.

MeSH Terms
Amino Acid Sequence Animals Crystallography, X-Ray Dimerization Hepatitis A Virus Cellular Receptor 1 Humans Immunity Membrane Proteins/chemistry,genetics,immunology Mice Molecular Sequence Data Protein Conformation Protein Structure, Tertiary Receptors, Immunologic/chemistry
Chemicals
Havcr1 protein, mouse Hepatitis A Virus Cellular Receptor 1 Membrane Proteins Receptors, Immunologic Timd2 protein, mouse
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Santiago César
Centro Nacional de Biotecnologia, CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain.
Ballesteros Angela
Tami Cecilia
Martínez-Muñoz Laura
Kaplan Gerardo G
Casasnovas José M
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1074-7613
DOI
10.1016/j.immuni.2007.01.014
Published
2007-03-00
Pages
299-310
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC7111020
Subset
IM
Grants
NIAID NIH HHS · P01 AI054456 · United States
NIAID NIH HHS · P01 AI54456 · United States
Corrections
CommentIn
PMID: 17376389
External Links
PubMed source DOI: 10.1016/j.immuni.2007.01.014 PMC Full Text View journal details
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