Transmembrane domains of the syndecan family of growth factor coreceptors display a hierarchy of homotypic and heterotypic interactions.
The single-pass transmembrane domains (TMDs) of the syndecan family of cell surface adhesion molecules have been implicated in functional protein-protein interactions. Although each paralog contains a conserved GxxxG dimerization motif, we show here that the syndecan-1 TMD dimerizes weakly, the syndecan-3 and syndecan-4 TMDs each dimerize strongly, and the syndecan-2 TMD dimerizes very strongly. These markedly different levels of self-association suggest that paralog TMDs play different roles in directing functional interactions of each full-length syndecan family member. We further show that each syndecan TMD forms detergent-resistant heteromeric complexes with other paralogs, and that these interactions exhibit selectivity. Although heteromeric interactions among full-length syndecan paralogs have not been reported, we argue that the distinct hierarchy of protein-protein interactions mediated by the syndecan TMDs may give rise to considerable complexity in syndecan function. The demonstration that TMD homodimerization and heterodimerization can be mediated by GxxxG motifs and modulated by sequence context has implications for the signaling mechanisms of other cell surface receptors, including the integrins and the erbB family.
Dews
Ian C
IC
Department of Biochemistry and Cell Biology, Rice University, 6100 Main Street, Houston, TX 77005, USA.
Mackenzie
Kevin R
KR
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D019281:Dimerization; D029968:Escherichia coli Proteins / Q000737:chemistry; D005816:Genetic Complementation Test; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D033902:Periplasmic Binding Proteins / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D053667:Syndecans / Q000737:chemistry*
D029968:Escherichia coli Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D033902:Periplasmic Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D053667:Syndecans; C461619:MalE protein, E coli; C508053:ERBB2 protein, human