Solution structure of a novel T-cell adhesion inhibitor derived from the fragment of ICAM-1 receptor: cyclo(1,8)-Cys-Pro-Arg-Gly-Gly-Ser-Val-Cys

This study is aimed at elucidating the structure of a novel T-cell adhesion inhibitor, cyclo(1,8)-CPRGGSVC using one- and two-dimensional 1H NMR and molecular dynamics (MD) simulation. The peptide is derived from the sequence of its parent peptide cIBR (cyclo(1,12)-PenPRGGSVLVTGC), which is a fragme...

Full description

Bibliographic Details
Main Authors: Tejo, Bimo Ario, Siahaan, Teruna A.
Format: Article
Language:English
English
Published: Wiley-Blackwell 2009
Subjects:
Online Access:http://psasir.upm.edu.my/id/eprint/16772/
http://psasir.upm.edu.my/id/eprint/16772/1/Solution%20structure%20of%20a%20novel%20T.pdf
_version_ 1848843055071756288
author Tejo, Bimo Ario
Siahaan, Teruna A.
author_facet Tejo, Bimo Ario
Siahaan, Teruna A.
author_sort Tejo, Bimo Ario
building UPM Institutional Repository
collection Online Access
description This study is aimed at elucidating the structure of a novel T-cell adhesion inhibitor, cyclo(1,8)-CPRGGSVC using one- and two-dimensional 1H NMR and molecular dynamics (MD) simulation. The peptide is derived from the sequence of its parent peptide cIBR (cyclo(1,12)-PenPRGGSVLVTGC), which is a fragment of intercellular adhesion molecule-1 (ICAM-1). Our previous results show that the cyclo(1,8)-CPRGGSVC peptide binds to the LFA-1 I-domain and inhibits heterotypic T-cell adhesion, presumably by blocking the LFA-1/ICAM-1 interactions. The structure of the peptide was determined using NMR and MD simulation in aqueous solution. Our results indicate that the peptide adopts type-I β-turn conformation at the Pro2-Arg3-Gly4-Gly5 (PRGG) sequence. The β-turn structure at the PRGG motif is well conserved in cIBR peptide and ICAM-1 receptor, which suggests the importance of the PRGG motif for the biological activity of cyclo(1,8)-CPRGGSVC peptide. Meanwhile, the Gly5-Ser6-Val7-Cys8-Cys1 (GSVCC) sequence forms a “turn-like” random coil structure that does not belong to any structured motif. Therefore, cyclo(1,8)-CPRGGSVC peptide has only one structured region at the PRGG sequence, which may play an important role in the binding of the peptide to the LFA-1 I-domain. The conserved β-turn conformation of the PRGG motif in ICAM-1, cIBR, and cyclo(1,8)-CPRGGSVC peptides can potentially be used to design peptidomimetics.
first_indexed 2025-11-15T08:08:56Z
format Article
id upm-16772
institution Universiti Putra Malaysia
institution_category Local University
language English
English
last_indexed 2025-11-15T08:08:56Z
publishDate 2009
publisher Wiley-Blackwell
recordtype eprints
repository_type Digital Repository
spelling upm-167722016-01-19T03:33:23Z http://psasir.upm.edu.my/id/eprint/16772/ Solution structure of a novel T-cell adhesion inhibitor derived from the fragment of ICAM-1 receptor: cyclo(1,8)-Cys-Pro-Arg-Gly-Gly-Ser-Val-Cys Tejo, Bimo Ario Siahaan, Teruna A. This study is aimed at elucidating the structure of a novel T-cell adhesion inhibitor, cyclo(1,8)-CPRGGSVC using one- and two-dimensional 1H NMR and molecular dynamics (MD) simulation. The peptide is derived from the sequence of its parent peptide cIBR (cyclo(1,12)-PenPRGGSVLVTGC), which is a fragment of intercellular adhesion molecule-1 (ICAM-1). Our previous results show that the cyclo(1,8)-CPRGGSVC peptide binds to the LFA-1 I-domain and inhibits heterotypic T-cell adhesion, presumably by blocking the LFA-1/ICAM-1 interactions. The structure of the peptide was determined using NMR and MD simulation in aqueous solution. Our results indicate that the peptide adopts type-I β-turn conformation at the Pro2-Arg3-Gly4-Gly5 (PRGG) sequence. The β-turn structure at the PRGG motif is well conserved in cIBR peptide and ICAM-1 receptor, which suggests the importance of the PRGG motif for the biological activity of cyclo(1,8)-CPRGGSVC peptide. Meanwhile, the Gly5-Ser6-Val7-Cys8-Cys1 (GSVCC) sequence forms a “turn-like” random coil structure that does not belong to any structured motif. Therefore, cyclo(1,8)-CPRGGSVC peptide has only one structured region at the PRGG sequence, which may play an important role in the binding of the peptide to the LFA-1 I-domain. The conserved β-turn conformation of the PRGG motif in ICAM-1, cIBR, and cyclo(1,8)-CPRGGSVC peptides can potentially be used to design peptidomimetics. Wiley-Blackwell 2009-08 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/16772/1/Solution%20structure%20of%20a%20novel%20T.pdf Tejo, Bimo Ario and Siahaan, Teruna A. (2009) Solution structure of a novel T-cell adhesion inhibitor derived from the fragment of ICAM-1 receptor: cyclo(1,8)-Cys-Pro-Arg-Gly-Gly-Ser-Val-Cys. Biopolymers, 91 (8). pp. 633-641. ISSN 0006-3525 Autoimmune diseases T cells Immunity 10.1002/bip.21192 English
spellingShingle Autoimmune diseases
T cells
Immunity
Tejo, Bimo Ario
Siahaan, Teruna A.
Solution structure of a novel T-cell adhesion inhibitor derived from the fragment of ICAM-1 receptor: cyclo(1,8)-Cys-Pro-Arg-Gly-Gly-Ser-Val-Cys
title Solution structure of a novel T-cell adhesion inhibitor derived from the fragment of ICAM-1 receptor: cyclo(1,8)-Cys-Pro-Arg-Gly-Gly-Ser-Val-Cys
title_full Solution structure of a novel T-cell adhesion inhibitor derived from the fragment of ICAM-1 receptor: cyclo(1,8)-Cys-Pro-Arg-Gly-Gly-Ser-Val-Cys
title_fullStr Solution structure of a novel T-cell adhesion inhibitor derived from the fragment of ICAM-1 receptor: cyclo(1,8)-Cys-Pro-Arg-Gly-Gly-Ser-Val-Cys
title_full_unstemmed Solution structure of a novel T-cell adhesion inhibitor derived from the fragment of ICAM-1 receptor: cyclo(1,8)-Cys-Pro-Arg-Gly-Gly-Ser-Val-Cys
title_short Solution structure of a novel T-cell adhesion inhibitor derived from the fragment of ICAM-1 receptor: cyclo(1,8)-Cys-Pro-Arg-Gly-Gly-Ser-Val-Cys
title_sort solution structure of a novel t-cell adhesion inhibitor derived from the fragment of icam-1 receptor: cyclo(1,8)-cys-pro-arg-gly-gly-ser-val-cys
topic Autoimmune diseases
T cells
Immunity
url http://psasir.upm.edu.my/id/eprint/16772/
http://psasir.upm.edu.my/id/eprint/16772/
http://psasir.upm.edu.my/id/eprint/16772/1/Solution%20structure%20of%20a%20novel%20T.pdf