Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, room 211-2, 4301 West Markham Street, #505, Little Rock, AR, 72205-7199, USA.
Curr Osteoporos Rep. 2010 Jun;8(2):77-83. doi: 10.1007/s11914-010-0010-7.
The past 3 years have been exciting for collagen biologists and human geneticists studying the disease known as osteogenesis imperfecta (OI or brittle bone disease). Functional studies on cartilage-associated protein (Crtap) have identified it as an essential component of a heterotrimeric, endoplasmic reticulum resident complex responsible for collagen prolyl 3-hydroxylation and chaperone function. Importantly, human mutations in the CRTAP gene have been associated with recessive forms of OI. Although the function and in vivo biological significance of the 3-hydroxyproline modification are still poorly understood, studies on Crtap have led to the identification of additional genes in which mutations also cause recessive forms of OI. These discoveries have now focused the interest of geneticists on the endoplasmic reticulum that will require the help of biochemists to unravel the molecular dynamics and complexities of collagen folding.
过去 3 年，研究骨不全症（OI 或成骨不全症）的胶原生物学家和人类遗传学家感到非常兴奋。对软骨相关蛋白（Crtap）的功能研究将其鉴定为负责胶原蛋白脯氨酰 3-羟化和伴侣功能的异三聚体、内质网驻留复合物的必需组成部分。重要的是，人类 CRTAP 基因突变与 OI 的隐性形式有关。尽管 3-羟脯氨酸修饰的功能和体内生物学意义仍知之甚少，但对 Crtap 的研究导致了其他基因突变也导致 OI 隐性形式的基因的鉴定。这些发现现在使遗传学家对内质网产生了兴趣，这将需要生物化学家的帮助来揭示胶原蛋白折叠的分子动力学和复杂性。
