Nevzorov I A, Redwood C S, Levitskiĭ D I
Biofizika. 2008 Nov-Dec;53(6):917-21.
The mutation Arg91Gly (R91G) in beta-tropomyosin (beta-TM) is known to cause distal arthrogryposis, a severe congenital disorder of muscle tissues. To elucidate how this mutation affects the structural properties of beta-TM, the thermal unfolding of beta-TM carrying mutation Arg91Gly was compared with that of the wild type protein. It was shown by differential scanning calorimetry and circular dichroism that this point mutation dramatically decreases the thermal stability of a significant part of beta-TM (about a half of the molecule). This part of the beta-TM molecule carrying mutation R91G unfolds at approximately 28 degrees C, i.e., at a much lower temperature than the other part of the molecule, which unfolds at approximately 40 degrees C. Based on the comparison of the data obtained by differential scanning calorimetry with measurements of temperature dependence of pyrene excimer fluorescence, whose decrease reflects the dissociation of two beta-TM chains in the region of pyrene-labeled Cys-36, this thermal transition was assigned to the N-terminal part of beta-TM. Interestingly, the destabilizing effect of the mutation spreads along the coiled-coil assuming a high extent of cooperativity within this part of the beta-TM molecule.
已知β-原肌球蛋白（β-TM）中的Arg91Gly（R91G）突变会导致远端关节挛缩症，这是一种严重的肌肉组织先天性疾病。为了阐明这种突变如何影响β-TM的结构特性，将携带Arg91Gly突变的β-TM的热解折叠与野生型蛋白进行了比较。差示扫描量热法和圆二色性表明，这种点突变显著降低了β-TM很大一部分（约分子的一半）的热稳定性。携带R91G突变的β-TM分子的这一部分在约28℃时解折叠，即，在比分子的另一部分低得多的温度下解折叠，分子的另一部分在约40℃时解折叠。基于差示扫描量热法获得的数据与芘激基缔合物荧光的温度依赖性测量结果的比较，芘激基缔合物荧光的降低反映了芘标记的Cys-36区域中两条β-TM链的解离，这种热转变被归因于β-TM的N端部分。有趣的是，突变的去稳定作用沿着卷曲螺旋延伸，假设在β-TM分子的这一部分内具有高度的协同性。
