Direct measurements of heterotypic adhesion between the cell surface proteins CD2 and CD48

Boru Zhu, Elizabeth A. Davies, P. Anton Van der Merwe, Tammy Calvert, Deborah E Leckband

Research output: Contribution to journalArticle

Abstract

Direct force measurements were used to investigate the molecular mechanism of heterophilic adhesion between the murine T-cell adhesion glycoprotein CD2 and its ligand CD48. From the distance dependence of the protein-protein interaction potential, we demonstrate directly that the full-length extracellular domains adhere in a head-to-head orientation. The absence of long-range electrostatic protein-protein attraction further indicates that the salt bridges between the binding surfaces only influence the interaction at short range. Despite the loss of a stabilizing disulfide bond in domain 1 (D1) of CD2, adhesive failure occurs abruptly with no evidence of partial protein unfolding during detachment. Finally, these measurements between extended membrane surfaces directly confirm that the low-affinity CD2-CD48 bond generates weak adhesion and that lateral receptor mobility is required for the development of appreciable adhesion. This is the first direct measurement of the range and magnitude of the forces governing heterotypic adhesion mediated by cell surface proteins. These results both verified the head-to-head CD2-CD48 docking alignment and demonstrated the ability to elucidate the structure -function relationships of adhesion proteins from the measured distance dependence of their interaction potentials.

Original languageEnglish (US)
Pages (from-to)12163-12170
Number of pages8
JournalBiochemistry
Volume41
Issue number40
DOIs
StatePublished - Oct 8 2002

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Membrane Proteins
Adhesion
Proteins
Protein Unfolding
Static Electricity
T-cells
Cell Adhesion
Force measurement
Disulfides
Adhesives
Cell adhesion
Glycoproteins
Salts
Electrostatics
Ligands
T-Lymphocytes
Membranes

ASJC Scopus subject areas

  • Biochemistry

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Direct measurements of heterotypic adhesion between the cell surface proteins CD2 and CD48. / Zhu, Boru; Davies, Elizabeth A.; Van der Merwe, P. Anton; Calvert, Tammy; Leckband, Deborah E.

In: Biochemistry, Vol. 41, No. 40, 08.10.2002, p. 12163-12170.

Research output: Contribution to journalArticle

Zhu, Boru ; Davies, Elizabeth A. ; Van der Merwe, P. Anton ; Calvert, Tammy ; Leckband, Deborah E. / Direct measurements of heterotypic adhesion between the cell surface proteins CD2 and CD48. In: Biochemistry. 2002 ; Vol. 41, No. 40. pp. 12163-12170.
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