The three-dimensional structure of an H-2Ld-peptide complex explains the unique interaction of Ld with beta-2 microglobulin and peptide

Ganesaratnam K. Balendiran, Joyce C. Solheim, Aideen C.M. Young, Ted H. Hansen, Stanley G. Nathenson, James C. Sacchettini

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Solution at 2.5-Å resolution of the three-dimensional structure of H-2Ld with a single nine-residue peptide provides a structural basis for understanding its unique interaction with beta-2 microglobulin (β2m) and peptide. Consistent with the biological data that show an unusually weak association of Ld with β2m, a novel orientation of the α1/α2 domains of Ld relative to β2m results in a dearth of productive contacts compared with other class I proteins. Characteristics of the Ld antigen-binding cleft determine the unique motif of peptides that it binds. Ld has no central anchor residue due to the presence of several bulky side chains in its mid-cleft region. Also, its cleft is significantly more Hydrophobic than that of the other class I molecules for which structures are known, resulting in many fewer H-bonds between peptide and cleft residues. The choice of Pro as a consensus anchor at peptide position 2 appears to be related to the hydrophobicity of the B pocket, and to the unique occurrence of Ile (which mirrors Pro in its inability to form H-bonds) at position 63 on the edge of this pocket. Thus, the paucity of stabilizing H-bonds combined with poor complementarity between peptide postion 2 Pro and the B pocket contribute to the weak association between Ld and its peptide antigen. The unique structural interactions of Ld with β2m and peptide could make Ld more suited than other classical class I molecules to play a role in alternative pathways of antigen presentation.

Original languageEnglish (US)
Pages (from-to)6880-6885
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number13
StatePublished - Jun 24 1997

Fingerprint

beta 2-Microglobulin
Peptides
Antigens
Antigen Presentation
Hydrophobic and Hydrophilic Interactions

ASJC Scopus subject areas

  • General

Cite this

The three-dimensional structure of an H-2Ld-peptide complex explains the unique interaction of Ld with beta-2 microglobulin and peptide. / Balendiran, Ganesaratnam K.; Solheim, Joyce C.; Young, Aideen C.M.; Hansen, Ted H.; Nathenson, Stanley G.; Sacchettini, James C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 13, 24.06.1997, p. 6880-6885.

Research output: Contribution to journalArticle

Balendiran, Ganesaratnam K. ; Solheim, Joyce C. ; Young, Aideen C.M. ; Hansen, Ted H. ; Nathenson, Stanley G. ; Sacchettini, James C. / The three-dimensional structure of an H-2Ld-peptide complex explains the unique interaction of Ld with beta-2 microglobulin and peptide. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 13. pp. 6880-6885.
@article{7e9c0f02fb9e4ad280ceae61a3b0c891,
title = "The three-dimensional structure of an H-2Ld-peptide complex explains the unique interaction of Ld with beta-2 microglobulin and peptide",
abstract = "Solution at 2.5-{\AA} resolution of the three-dimensional structure of H-2Ld with a single nine-residue peptide provides a structural basis for understanding its unique interaction with beta-2 microglobulin (β2m) and peptide. Consistent with the biological data that show an unusually weak association of Ld with β2m, a novel orientation of the α1/α2 domains of Ld relative to β2m results in a dearth of productive contacts compared with other class I proteins. Characteristics of the Ld antigen-binding cleft determine the unique motif of peptides that it binds. Ld has no central anchor residue due to the presence of several bulky side chains in its mid-cleft region. Also, its cleft is significantly more Hydrophobic than that of the other class I molecules for which structures are known, resulting in many fewer H-bonds between peptide and cleft residues. The choice of Pro as a consensus anchor at peptide position 2 appears to be related to the hydrophobicity of the B pocket, and to the unique occurrence of Ile (which mirrors Pro in its inability to form H-bonds) at position 63 on the edge of this pocket. Thus, the paucity of stabilizing H-bonds combined with poor complementarity between peptide postion 2 Pro and the B pocket contribute to the weak association between Ld and its peptide antigen. The unique structural interactions of Ld with β2m and peptide could make Ld more suited than other classical class I molecules to play a role in alternative pathways of antigen presentation.",
author = "Balendiran, {Ganesaratnam K.} and Solheim, {Joyce C.} and Young, {Aideen C.M.} and Hansen, {Ted H.} and Nathenson, {Stanley G.} and Sacchettini, {James C.}",
year = "1997",
month = "6",
day = "24",
language = "English (US)",
volume = "94",
pages = "6880--6885",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "13",

}

TY - JOUR

T1 - The three-dimensional structure of an H-2Ld-peptide complex explains the unique interaction of Ld with beta-2 microglobulin and peptide

AU - Balendiran, Ganesaratnam K.

AU - Solheim, Joyce C.

AU - Young, Aideen C.M.

AU - Hansen, Ted H.

AU - Nathenson, Stanley G.

AU - Sacchettini, James C.

PY - 1997/6/24

Y1 - 1997/6/24

N2 - Solution at 2.5-Å resolution of the three-dimensional structure of H-2Ld with a single nine-residue peptide provides a structural basis for understanding its unique interaction with beta-2 microglobulin (β2m) and peptide. Consistent with the biological data that show an unusually weak association of Ld with β2m, a novel orientation of the α1/α2 domains of Ld relative to β2m results in a dearth of productive contacts compared with other class I proteins. Characteristics of the Ld antigen-binding cleft determine the unique motif of peptides that it binds. Ld has no central anchor residue due to the presence of several bulky side chains in its mid-cleft region. Also, its cleft is significantly more Hydrophobic than that of the other class I molecules for which structures are known, resulting in many fewer H-bonds between peptide and cleft residues. The choice of Pro as a consensus anchor at peptide position 2 appears to be related to the hydrophobicity of the B pocket, and to the unique occurrence of Ile (which mirrors Pro in its inability to form H-bonds) at position 63 on the edge of this pocket. Thus, the paucity of stabilizing H-bonds combined with poor complementarity between peptide postion 2 Pro and the B pocket contribute to the weak association between Ld and its peptide antigen. The unique structural interactions of Ld with β2m and peptide could make Ld more suited than other classical class I molecules to play a role in alternative pathways of antigen presentation.

AB - Solution at 2.5-Å resolution of the three-dimensional structure of H-2Ld with a single nine-residue peptide provides a structural basis for understanding its unique interaction with beta-2 microglobulin (β2m) and peptide. Consistent with the biological data that show an unusually weak association of Ld with β2m, a novel orientation of the α1/α2 domains of Ld relative to β2m results in a dearth of productive contacts compared with other class I proteins. Characteristics of the Ld antigen-binding cleft determine the unique motif of peptides that it binds. Ld has no central anchor residue due to the presence of several bulky side chains in its mid-cleft region. Also, its cleft is significantly more Hydrophobic than that of the other class I molecules for which structures are known, resulting in many fewer H-bonds between peptide and cleft residues. The choice of Pro as a consensus anchor at peptide position 2 appears to be related to the hydrophobicity of the B pocket, and to the unique occurrence of Ile (which mirrors Pro in its inability to form H-bonds) at position 63 on the edge of this pocket. Thus, the paucity of stabilizing H-bonds combined with poor complementarity between peptide postion 2 Pro and the B pocket contribute to the weak association between Ld and its peptide antigen. The unique structural interactions of Ld with β2m and peptide could make Ld more suited than other classical class I molecules to play a role in alternative pathways of antigen presentation.

UR - http://www.scopus.com/inward/record.url?scp=0030917013&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030917013&partnerID=8YFLogxK

M3 - Article

C2 - 9192660

AN - SCOPUS:0030917013

VL - 94

SP - 6880

EP - 6885

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 13

ER -