Disulfide bond formation promotes the cis- and trans-dimerization of the E-cadherin-derived first repeat.
Cadherin is a cell adhesion molecule crucial for epithelial and endothelial cell monolayer integrity. The previously solved x-ray crystallographic structure of the E-CAD12 cis-dimer displayed an unpaired Cys(9), which protruded away from the Cys(9) on the other protomer. To investigate the possible biological function of Cys(9) within the first repeat (the E-cadherin-derived N-terminal repeat), E-CAD1 was overexpressed and secreted into the periplasmic space of Escherichia coli cells. Recombinant E-CAD1 produced a mixed monomer and dimer in an equilibrium fashion. The dimer was linked by a disulfide through Cys(9) pairing. Analysis by high pressure liquid chromatography and electron microscopy suggested the existence of oligomeric complexes. Mutation at Trp(2) appears to indicate that these oligomeric complexes trans-dimerize. Interestingly, mutation of Cys(9) affected not only the cis-dimerization, but also the trans-oligomerization of E-CAD1. Accordingly, it is plausible that, under oxidative stress, the homophilic interactions of E-cadherin through E-CAD1 may be promoted and stabilized by this disulfide bond.
Makagiansar
Irwan T
IT
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
Nguyen
Phuong D
PD
Ikesue
Atsutoshi
A
Kuczera
Krzysztof
K
Dentler
William
W
Urbauer
Jeffrey L
JL
Galeva
Nadezhda
N
Alterman
Michail
M
Siahaan
Teruna J
TJ
D000595:Amino Acid Sequence; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D019281:Dimerization; D004220:Disulfides / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
D015820:Cadherins; D004220:Disulfides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins