Dynamic characterisation of the netrin-like domain of human type 1 procollagen C-proteinase enhancer and comparison to the N-terminal domain of tissue inhibitor of metalloproteinases (TIMP).
The backbone mobility of the C-terminal domain of procollagen C-proteinase enhancer (NTR PCOLCE1), part of a connective tissue glycoprotein, was determined using 15N NMR spectroscopy. NTR PCOLCE1 has been shown to be a netrin-like domain and adopts an OB-fold such as that found in the N-terminal domain of tissue inhibitors of metalloproteinases-1 (N-TIMP-1), N-TIMP-2, the laminin-binding domain of agrin and the C-terminal domain of complement protein C5. NMR relaxation dynamics of NTR PCOLCE1 highlight conformational flexibility in the N-terminus, strand A and the proximal CD loop. This region in N-TIMP is known to be essential for inhibitory activity against the matrix metalloproteinases and suggests that this region is of equal importance for NTR PCOLCE1, although the specific functional activity of the NTR PCOLCE1 domain is still unknown. Dynamics observed within the structural core of NTR PCOLCE1 that are not observed in N-TIMP molecules suggest that although the two domains have a similar architecture, the NTR PCOLCE1 domain will show different thermodynamic properties on binding and hence the target molecule could be somewhat different from that observed for the TIMPs. ModelFree order parameters show that NTR PCOLCE1 has more flexibility than both N-TIMP-1 and N-TIMP-2.
Williamson
Richard A
RA
Department of Biosciences, University of Kent, Canterbury, Kent, UK. r.a.williamson@kent.ac.uk
Panagiotidou
Parthena
P
Mott
Joni D
JD
Howard
Mark J
MJ
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D006023:Glycoproteins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D000075386:Netrin Receptors; D017510:Protein Folding; D011498:Protein Precursors / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry*; D016415:Sequence Alignment; D019714:Tissue Inhibitor of Metalloproteinases / Q000737:chemistry*
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D000075386:Netrin Receptors; C491555:PCOLCE protein, human; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D019714:Tissue Inhibitor of Metalloproteinases