Page Richard C, Clark Jeffrey G, Misra Saurav
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Aug 1;67(Pt 8):871-6. doi: 10.1107/S1744309111024249. Epub 2011 Jul 26.
Filamin A (FlnA) plays a critical role in cytoskeletal organization, cell motility and cellular signaling. FlnA utilizes different binding sites on a series of 24 immunoglobulin-like domains (Ig repeats) to interact with diverse cytosolic proteins and with cytoplasmic portions of membrane proteins. Mutations in a specific domain, Ig10 (FlnA-Ig10), are correlated with two severe forms of the otopalatodigital syndrome spectrum disorders Melnick-Needles syndrome and frontometaphyseal dysplasia. The crystal structure of FlnA-Ig10 determined at 2.44 Å resolution provides insight into the perturbations caused by these mutations.
细丝蛋白A（FlnA）在细胞骨架组织、细胞运动和细胞信号传导中起着关键作用。FlnA利用一系列24个免疫球蛋白样结构域（Ig重复序列）上的不同结合位点，与多种胞质蛋白以及膜蛋白的胞质部分相互作用。特定结构域Ig10（FlnA-Ig10）中的突变与耳腭指综合征谱系疾病的两种严重形式——梅尼克-尼德尔斯综合征和额骨干骺端发育异常相关。以2.44Å分辨率测定的FlnA-Ig10晶体结构，为这些突变引起的扰动提供了深入了解。
