Fibrillin-1 interactions with fibulins depend on the first hybrid domain and provide an adaptor function to tropoelastin.
Fibrillin-containing microfibrils in elastic and nonelastic extracellular matrices play important structural and functional roles in various tissues, including blood vessels, lung, skin, and bone. Microfibrils are supramolecular aggregates of several protein and nonprotein components. Recently, a large region in the N-terminal portion of fibrillin-1 was characterized as a multifunctional protein interaction site, including binding sites for fibulin-2 and -5 among others. Using a panel of recombinant fibrillin-1 swapped domain and deletion fragments, we demonstrate here that the conserved first hybrid domain in fibrillin-1 is essential for binding to fibulin-2, -4, and -5. Fibulin-3 and various isoforms of fibulin-1 did not interact with fibrillin-1. Although the first hybrid domain in fibrillin-1 is located in close vicinity to the self-assembly epitope, binding of fibulin-2, -4, and -5 did not interfere with self-assembly. However, these fibulins can associate with microfibrils at various levels of maturity. Formation of ternary complexes between fibrillin-1, fibulins, and tropoelastin demonstrated that fibulin-2 and -5 but much less fibulin-4, are able to act as molecular adaptors between fibrillin-1 and tropoelastin.
El-Hallous
Ehab
E
Faculty of Medicine, Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 2B2, Canada.
Sasaki
Takako
T
Hubmacher
Dirk
D
Getie
Melkamu
M
Tiedemann
Kerstin
K
Brinckmann
Jürgen
J
Bätge
Boris
B
Davis
Elaine C
EC
Reinhardt
Dieter P
DP
D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000737:chemistry; D000071838:Fibrillin-1; D000071837:Fibrillins; D017353:Gene Deletion; D006801:Humans; D008024:Ligands; D008840:Microfilament Proteins / Q000737:chemistry*; D008954:Models, Biological; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D014333:Tropoelastin / Q000737:chemistry*; D054392:Adipokines
D002135:Calcium-Binding Proteins; D000939:Epitopes; D000071838:Fibrillin-1; D000071837:Fibrillins; D008024:Ligands; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D014333:Tropoelastin; C000605722:FBN1 protein, human; D054392:Adipokines; C060820:fibulin