Laidman Janel, Forse G Jason, Yeates Todd O
Department of Chemistry and Biochemistry, University of California-Los Angeles (UCLA), Post Office Box 951569, Los Angeles, CA 90095-1569, USA.
Acc Chem Res. 2006 Sep;39(9):576-83. doi: 10.1021/ar050017s.
Numerous diseases are characterized by the formation of insoluble, amyloid protein fibrils. Intensive investigations are beginning to unravel the detailed molecular and structural principles that underlie the spontaneous formation of these fibrils. The amyloid protein transthyretin serves as an excellent system for dissecting the conformational changes and ensuing subunit-subunit associations that lead to amyloid. One working model for tranthyretin amyloid involves the exposure of an "unprotected" edge beta strand, followed by symmetric assembly of subunits to give head-to-head and tail-to-tail protofibrils. The models and principles emerging from studies on transthyretin lead to connections to other amyloid systems.
许多疾病的特征是形成不溶性淀粉样蛋白纤维。深入研究开始揭示这些纤维自发形成背后的详细分子和结构原理。淀粉样蛋白转甲状腺素蛋白是剖析导致淀粉样变的构象变化及随后亚基-亚基缔合的绝佳系统。转甲状腺素蛋白淀粉样变的一个工作模型涉及“未受保护”的边缘β链的暴露，随后亚基对称组装形成头对头和尾对尾的原纤维。对转甲状腺素蛋白的研究中出现的模型和原理与其他淀粉样蛋白系统建立了联系。
