A sulfilimine bond identified in collagen IV.
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.
Vanacore
Roberto
R
Division of Nephrology, Department of Medicine and Center for Matrix Biology, Vanderbilt University, Nashville, TN 37232, USA. roberto.vanacore@vanderbilt.edu
Ham
Amy-Joan L
AJ
Voehler
Markus
M
Sanders
Charles R
CR
Conrads
Thomas P
TP
Veenstra
Timothy D
TD
Sharpless
K Barry
KB
Dawson
Philip E
PE
Hudson
Billy G
BG
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D024141:Collagen Type IV / Q000737:chemistry*; D006801:Humans; D006901:Hydroxylysine / Q000737:chemistry; D013058:Mass Spectrometry; D008715:Methionine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry; D016415:Sequence Alignment; D013314:Stress, Mechanical; D013455:Sulfur / Q000737:chemistry
D024141:Collagen Type IV; D021122:Protein Subunits; D006901:Hydroxylysine; D013455:Sulfur; D008715:Methionine; D009584:Nitrogen