Gly-Pro-Arg confers stability similar to Gly-Pro-Hyp in the collagen triple-helix of host-guest peptides.
A set of host-guest peptides of the form Ac(Gly-Pro-Hyp)3-Gly-X-Y-(Gly-Pro-Hyp)4-Gly-Gly-NH2 has been designed to evaluate the propensity of different Gly-X-Y triplets for the triple-helix conformation (Shah, N. K., Ramshaw, J. A. M., Kirkpatrick, A., Shah, C., and Brodsky, B. (1996) Biochemistry 35, 10262-10268). All Gly-X-Y guest triplets led to a decrease in melting temperature from the host (Gly-Pro-Hyp)8 peptide except for Gly-Pro-Arg. In this Gly-Pro-Hyp-rich environment, Gly-Pro-Arg was found to be as stabilizing as Gly-Pro-Hyp. Decreased stability of host-guest peptides containing Gly-Pro-Lys, Gly-Pro-homo-Arg, and Gly-Arg-Hyp compared with Gly-Pro-Arg indicated a stabilization that is optimal for Arg and specific to the Y-position. Arg was found to have a similar stabilizing effect when residues other than Pro are in the X-position. Both Arg and Hyp stabilize the triple-helix preferentially in the Y-position in a stereospecific manner and occupy largely Y-positions in collagen. However, contiguous Gly-Pro-Hyp units are highly stable and promote triple-helix folding, whereas incorporation of multiple Gly-Pro-Arg triplets was destabilizing and folded slowly due to charge repulsion. In collagen, Gly-Pro-Arg may contribute maximally to local triple-helix stability while also having the potential for electrostatic interactions in fibril formation and binding.
Yang
W
W
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854-5636, USA.
Chan
V C
VC
Kirkpatrick
A
A
Ramshaw
J A
JA
Brodsky
B
B
D000595:Amino Acid Sequence; D003094:Collagen / Q000737:chemistry*; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation
D009842:Oligopeptides; D010455:Peptides; C088188:glycyl-prolyl-hydroxyproline; C035024:glycyl-prolyl-arginine; D003094:Collagen