A Sulfilimine Bond Identified in Collagen IV
Roberto Vanacore,1,*
Amy-Joan L. Ham,2,
Markus Voehler,3
Charles R. Sanders,2
Thomas P. Conrads,5,
Timothy D. Veenstra,5
K. Barry Sharpless,6
Philip E. Dawson,6,7
Billy G. Hudson1,2,4,*
Collagen IV networks are ancient proteins of basement membranes
that underlie epithelia in metazoa from sponge to human. The
networks provide structural integrity to tissues and serve as
ligands for integrin cell-surface receptors. They are assembled
by oligomerization of triple-helical protomers and are covalently
crosslinked, a key reinforcement that stabilizes networks. We
used Fourier-transform ion cyclotron resonance mass spectrometry
and nuclear magnetic resonance spectroscopy to show that a sulfilimine
bond (-S=N-) crosslinks hydroxylysine-211 and methionine-93
of adjoining protomers, a bond not previously found in biomolecules.
This bond, the nitrogen analog of a sulfoxide, appears to have
arisen at the divergence of sponge and cnidaria, an adaptation
of the extracellular matrix in response to mechanical stress
in metazoan evolution.
2 Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
3 Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
4 Department of Pathology, Vanderbilt University, Nashville, TN 37232, USA.
5 Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick, Incorporated, National Cancer Institute, Frederick, MD 21702, USA.
6 Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
7 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Present address: Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Present address: Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
* To whom correspondence should be addressed. E-mail: roberto.vanacore{at}vanderbilt.edu (R.V.); billy.hudson{at}vanderbilt.edu (B.G.H.)
