Characteristics of type IV collagen unfolding under various pH conditions as a model of pathological disorder in tissue.
The overall structure of type IV collagen is the same at neutral and acidic pH, as determined by circular dichroism spectra. The heating rate dependence of denaturation midpoint temperature (T(m)) shows that type IV collagen is unstable at body temperature, similarly to type I collagen. The heating rate dependence of T(m) at neutral pH has two phases, but that at acidic pH apparently has a single phase. The T(m) of the first phase (lower T(m)) at neutral pH is consistent with that at acidic pH, and the activation energy of these phases is consistent, within experimental error. The triple helix region of type IV collagen corresponding to the second phase (higher T(m)) at neutral pH is thermally stable when compared to the triple helical structure at acidic pH. At acidic pH, as the loosely packed and unstable region has spread throughout the whole molecule, the thermal transition is thought to be cooperative and is observed as a single phase. Structural flexibility is related to protein function and assembly; therefore, the unstable structure and increased flexibility of type IV collagen induced at acidic pH may affect diseases accompanied by type IV collagen disorder.
Department of Environmental Engineering for Symbiosis, Faculty of Engineering, Soka University, Tokyo, Japan. shimizu@t.soka.ac.jp
Akio
A
Shimizu
Kenichi
K
Kawai
Miki
M
Yanagino
Toshiko
T
Wakiyama
Minoru
M
Machida
Kohji
K
Kameyama
Zenya
Z
Naito
D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D024141:Collagen Type IV / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D013696:Temperature; D013816:Thermodynamics; D014466:Ultraviolet Rays
D024141:Collagen Type IV