The role of the alpha2 chain in the stabilization of the collagen type I heterotrimer: a study of the type I homotrimer in oim mouse tissues.
We have previously reported that the fragility of skin, tendon and bone from the oim mouse is related to a significant reduction in the intermolecular cross-linking. The oim mutation is unlikely to affect the efficacy of the lysyl oxidase, suggesting that the defect is in the molecule and fibre. We have therefore investigated the integrity of both the oim collagen molecules and the fibre by differential scanning calorimetry. The denaturation temperature of the oim molecule in solution and the fibre from tail tendon were found to be higher than the wild-type by 2.6deg.C and 1.9deg.C, respectively. With the loss of the alpha2 chain, the hydroxyproline content of the homotrimer is higher than the heterotrimer, which may account for the increase. There is a small decrease in the enthalpy of the oim fibres but it is not significant, suggesting that the amount of disorder of the triple-helical molecules and of the fibres is small and involves only a small part of the total bond energy holding the helical structure together. The difference in denaturation temperature of the skin collagen molecules (t(m)) and fibres (t(d)) is significantly lower for the oim tissues, 19.9deg.C against 23.1deg.C, indicating reduced molecular interactions and hence packing of the molecules in the fibre. Computation of the volume fraction of the water revealed that the interaxial separation of the oim fibres was indeed greater, increasing from 19.6A to 21.0A. This difference of 1.4A, equivalent to a C-C bond, would certainly decrease the ability of the telopeptide aldehyde to interact with the epsilon -amino group from an adjacent molecule and form a cross-link. We suggest, therefore, that the reduction of the cross-linking is due to increased water content of the fibre rather than a distortion of the molecular structure. The higher hydrophobicity of the alpha2 chain appears to play a role in the stabilisation of heterotrimeric type I collagen, possibly by increasing the hydrophobic interactions between the heterotrimeric molecules, thereby reducing the water content and increasing the binding of the molecules in the fibre.
Collagen Research Group, Division of Molecular and Cellular Biology, University of Bristol, UK.
Christopher A
CA
Miles
Trevor J
TJ
Sims
Nancy P
NP
Camacho
Allen J
AJ
Bailey
D000818:Animals; D002152:Calorimetry, Differential Scanning; D003094:Collagen / Q000235:genetics* / Q000502:physiology*; D024042:Collagen Type I / Q000032:analysis / Q000737:chemistry* / Q000648:ultrastructure; D024061:Collagen Type III / Q000032:analysis; D006901:Hydroxylysine / Q000032:analysis; D051379:Mice; D008817:Mice, Mutant Strains; D011489:Protein Denaturation; D021122:Protein Subunits; D012867:Skin / Q000737:chemistry; D013623:Tail; D013710:Tendons / Q000737:chemistry
D024042:Collagen Type I; D024061:Collagen Type III; D021122:Protein Subunits; D006901:Hydroxylysine; D003094:Collagen