Mapping the Intercellular Adhesion Molecule-1 and -2 Binding Site on the Inserted Domain of Leukocyte Function-associated Antigen-1

Edwards, Caroline P.; Fisher, Karen L.; Presta, Leonard G.; Bodary, Sarah C.

doi:10.1074/jbc.273.44.28937

Cited by 49 publications

(51 citation statements)

References 50 publications

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“…Comparison of the unbound ␣ 2 A-domain with the recently crystallized complex of this A-domain bound to a collagenous triple peptide confirms the model (31). This complex and mutational analyses of the ␣ 2 , ␣ L , and ␣ M integrins have revealed other residues on the upper surface of the A-domains surrounding the MIDAS cleft that contribute to the affinity and specificity of ligand binding (26,29,(32)(33)(34).…”

supporting

confidence: 57%

“…The equivalent of Phe 298 in ␣ L , Thr 243 , is involved in binding to ICAM-1 and -2, but forms part of a relatively flat binding surface (20,32,33), and His 258 of ␣ 2 is involved in collagen I binding, but forms a hydrogen bond with the main chain of collagen (31,34). Also, the ␣ 1 and ␣ 2 integrin A-domains contain an extra four-amino acid ␣-C helix in the ␤ E -␣ 6 loop that markedly alters the topology of the A-domain surface and regulates access to the collagen-binding site (21,22,31,34,80).…”

Section: Discussionmentioning

confidence: 99%

“…␣ M integrins have revealed other residues on the upper surface of the A-domains surrounding the MIDAS cleft that contribute to the affinity and specificity of ligand binding (26,29,(32)(33)(34). This mechanism provides an elegant explanation of ligand binding by A-domain-containing integrins.…”

mentioning

confidence: 99%

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The Role of α and β Chains in Ligand Recognition by β7 Integrins

Higgins¹,

Cernadas²,

Tan³

et al. 2000

Journal of Biological Chemistry

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Integrins ␣ E ␤ 7 and ␣ 4 ␤ 7 are involved in localization of leukocytes at mucosal sites. Although both ␣ E ␤ 7 and ␣ 4 ␤ 7 utilize the ␤ 7 chain, they have distinct binding specificities for E-cadherin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1), respectively. We found that mutation of the metal ion-dependent adhesion site (MIDAS) in the ␣ E A-domain (D190A) abolished E-cadherin binding, as did mutation F298A on the A-domain surface near the MIDAS cleft. A docking model of the A-domain with E-cadherin domain 1 indicates that coordination of the ␣ E MIDAS metal ion by E-cadherin Glu 31 and a novel projection of Phe 298 into a hydrophobic pocket on E-cadherin provide the basis for the interaction. The location of the binding site on the ␣ E A-domain resembles that on other integrins, but its structure appears distinctive and particularly adapted to recognize the tip of E-cadherin, a unique integrin ligand. Additionally, mutation of the ␤ 7 MIDAS motif (D140A) abolished ␣ E ␤ 7 binding to E-cadherin and ␣ 4 ␤ 7 -mediated adhesion to MAdCAM-1, and ␣ 4 chain mutations that abrogated binding of ␣ 4 ␤ 1 to vascular cell adhesion molecule-1 and fibronectin similarly reduced ␣ 4 ␤ 7 interaction with MAdCAM-1. Thus, although specificity can be determined by the integrin ␣ or ␤ chain, common structural features of both subunits are required for recognition of dissimilar ligands.Integrins are heterodimeric glycoproteins consisting of noncovalently associated ␣ and ␤ subunits that play diverse roles in cell-cell and cell-matrix interactions. Integrins of the ␤ 1 , ␤ 2 , and ␤ 7 subfamilies are critical for leukocyte homing (1, 2). For example, binding of integrin ␣ 4 ␤ 7 to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) 1 on intestinal endothelial cells is required for the homing of naive lymphocytes to Peyer's patches (2). Integrins are also thought to play a role in microenvironmental homing or retention of lymphocytes at particular sites within a tissue (2). For instance, integrin ␣ E ␤ 7 binds to epithelial cadherin (E-cadherin) and is involved in retention of lymphocytes within the epithelium (3-6).Many integrin ligands are members of the immunoglobulin superfamily (such as VCAM-1 and MAdCAM-1) or possess domains that resemble the immunoglobulin fold (e.g. E-cadherin and the type III repeats of fibronectin). A unifying feature of these ligands is an integrin-binding surface containing an exposed acidic amino acid. For example, ␣ 4 ␤ 1 and ␣ 4 ␤ 7 bind to VCAM-1 and MAdCAM-1, respectively, on the face of domain 1 formed by the C, F, and G ␤-strands, centered on an aspartate residue in the loop connecting the C and D strands (7-9). Domain 1 of E-cadherin contains a glutamate residue at the tip of the BC-loop essential for ␣ E ␤ 7 binding (10,11), and the tenth type III repeat of fibronectin has an acidic residue within an RGD sequence on the FG-loop required for ␣ 5 ␤ 1 binding (12). Other integrin ligands such as collagen I and iC3b that are not known to adopt immunoglobulin-like folds also possess...

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supporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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The Role of α and β Chains in Ligand Recognition by β7 Integrins

Higgins¹,

Cernadas²,

Tan³

et al. 2000

Journal of Biological Chemistry

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“…The 1ido and 1jlm Side chains of residues important in binding to ICAM-1 and ICAM-2 are shown with rose-pink side chains and yellow sulfur, red oxygen, and blue nitrogen atoms. These residues, defined as important in species-specific binding to ICAM-1 (43) or by at least a 2-fold effect on binding to ICAM-1 or ICAM-2 upon mutation to alanine (44), are M140, E146, T175, L205, E241, T243, S245, and K263. Note that these residues surround the Mg 2ϩ ion and are distant from the disulfide.…”

Section: Methodsmentioning

confidence: 99%

Reversibly locking a protein fold in an active conformation with a disulfide bond: Integrin αL I domains with high affinity and antagonist activityin vivo

Shimaoka

Palframan

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

212

258

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“…In some integrins, including the four ␤2 integrins, a structurally characterized inserted (I) domain (19) of Ϸ200 residues exists between repeats 2 and 3, positioned on top of the ␤-propeller (18). In LFA-1 (␣L␤2), the I domain has been shown to directly mediate conformation-and cation-dependent ICAM-1-binding through its metal ion-dependent adhesion site (20)(21)(22)(23).…”

mentioning

confidence: 99%