'American Society for Biochemistry & Molecular Biology (ASBMB)'
Doi
Abstract
The extracellular matrix protein EMILIN1 (elastin microfi-
bril interface located protein 1) is implicated in maintaining
blood pressure homeostasis via the N-terminal elastin microfi-
bril interface domain and in trophoblast invasion of the uterine
wall via the globular C1q (gC1q) domain. Here, we describe the
first NMR-based homology model structure of the human
52-kDa homotrimer of the EMILIN1 gC1q domain. In contrast
to all of the gC1q (crystal) structures solved to date, the
10-stranded \u2424-sandwich fold of the gC1q domain is reduced to
nine \u2424 strands with a consequent increase in the size of the cen-
tral cavity lumen. An unstructured loop, resulting from an inser-
tion unique to EMILIN1 and EMILIN2 family members and
located at the trimer apex upstream of the missing strand, spe-
cifically engages the \u24234\u24241 integrin. Using both Jurkat T and
EA.hy926 endothelial cells as well as site-directed mutagenesis,
we demonstrate that the ability of \u24234\u24241 integrins to recognize
the trimeric EMILIN1 gC1q domain mainly depends on a single
glutamic acid residue (Glu933). Static and flow adhesion of T
cells and haptotactic migration of endothelial cells on gC1q is
fully dependent on this residue. Thus, EMILIN1 gC1q-\u24234\u24241
represents a unique ligand/receptor system, with a requirement
for a 3-fold arrangement of the interaction site