Song Jikui, McGivern Jered V, Nichols Karl W, Markley John L, Sheets Michael D
Department of Biochemistry, Center for Eukaryotic Structural Genomics, University of Wisconsin, Madison, WI 53706, USA.
Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15317-22. doi: 10.1073/pnas.0801274105. Epub 2008 Sep 29.
We identified a functional domain (XlePABP2-TRP) of Xenopus laevis embryonic type II poly(A)-binding protein (XlePABP2). The NMR structure of XlePABP2-TRP revealed that the protein is a homodimer formed by the antiparallel association of beta-strands from the single RNA recognition motif (RRM) domain of each subunit. In each subunit of the homodimer, the canonical RNA recognition site is occluded by a polyproline motif. Upon poly(A) binding, XlePABP2-TRP undergoes a dimer-monomer transition that removes the polyproline motif from the RNA recognition site and allows it to be replaced by the adenosine nucleotides of poly(A). Our results provide high-resolution structural information concerning type II PABPs and an example of a single RRM domain protein that transitions from a homodimer to a monomer upon RNA binding. These findings advance our understanding of RRM domain regulation, poly(A) recognition, and are relevant to understanding how type II PABPs function in mRNA processing and human disease.
我们鉴定出了非洲爪蟾胚胎II型聚腺苷酸结合蛋白(XlePABP2)的一个功能结构域(XlePABP2-TRP)。XlePABP2-TRP的核磁共振结构显示,该蛋白是一个同型二聚体,由每个亚基的单个RNA识别基序(RRM)结构域中的β链反平行缔合形成。在同型二聚体的每个亚基中,典型的RNA识别位点被一个多聚脯氨酸基序所遮蔽。在结合聚腺苷酸后,XlePABP2-TRP会发生二聚体-单体转变,将多聚脯氨酸基序从RNA识别位点移除,并使其被聚腺苷酸的腺苷核苷酸取代。我们的结果提供了关于II型聚腺苷酸结合蛋白的高分辨率结构信息,以及一个单一RRM结构域蛋白在结合RNA后从同型二聚体转变为单体的例子。这些发现推进了我们对RRM结构域调控、聚腺苷酸识别的理解,并且与理解II型聚腺苷酸结合蛋白在mRNA加工和人类疾病中的功能相关。