Three-dimensional EM structure of the ectodomain of integrin αVβ3 in a complex with fibronectin
BD Adair, JP Xiong, C Maddock, SL Goodman… - The Journal of cell …, 2005 - rupress.org
BD Adair, JP Xiong, C Maddock, SL Goodman, MA Arnaout, M Yeager
The Journal of cell biology, 2005•rupress.orgIntegrins are αβ heterodimeric cell surface receptors that mediate transmembrane signaling
by binding extracellular and cytoplasmic ligands. The ectodomain of integrin αVβ3
crystallizes in a bent, genuflexed conformation considered to be inactive (unable to bind
physiological ligands in solution) unless it is fully extended by activating stimuli. We
generated a stable, soluble complex of the Mn2+-bound αVβ3 ectodomain with a fragment
of fibronectin (FN) containing type III domains 7 to 10 and the EDB domain (FN7-EDB-10) …
by binding extracellular and cytoplasmic ligands. The ectodomain of integrin αVβ3
crystallizes in a bent, genuflexed conformation considered to be inactive (unable to bind
physiological ligands in solution) unless it is fully extended by activating stimuli. We
generated a stable, soluble complex of the Mn2+-bound αVβ3 ectodomain with a fragment
of fibronectin (FN) containing type III domains 7 to 10 and the EDB domain (FN7-EDB-10) …
Integrins are αβ heterodimeric cell surface receptors that mediate transmembrane signaling by binding extracellular and cytoplasmic ligands. The ectodomain of integrin αVβ3 crystallizes in a bent, genuflexed conformation considered to be inactive (unable to bind physiological ligands in solution) unless it is fully extended by activating stimuli. We generated a stable, soluble complex of the Mn2+-bound αVβ3 ectodomain with a fragment of fibronectin (FN) containing type III domains 7 to 10 and the EDB domain (FN7-EDB-10). Transmission electron microscopy and single particle image analysis were used to determine the three-dimensional structure of this complex. Most αVβ3 particles, whether unliganded or FN-bound, displayed compact, triangular shapes. A difference map comparing ligand-free and FN-bound αVβ3 revealed density that could accommodate the RGD-containing FN10 in proximity to the ligand-binding site of β3, with FN9 just adjacent to the synergy site binding region of αV. We conclude that the ectodomain of αVβ3 manifests a bent conformation that is capable of stably binding a physiological ligand in solution.
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