1si2
Crystal structure of the PAZ domain of human eIF2c1 in complex with a 9-mer siRNA-like duplex of deoxynucleotide overhangCrystal structure of the PAZ domain of human eIF2c1 in complex with a 9-mer siRNA-like duplex of deoxynucleotide overhang
Structural highlights
Function[AGO1_HUMAN] Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs).[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedShort RNAs mediate gene silencing, a process associated with virus resistance, developmental control and heterochromatin formation in eukaryotes. RNA silencing is initiated through Dicer-mediated processing of double-stranded RNA into small interfering RNA (siRNA). The siRNA guide strand associates with the Argonaute protein in silencing effector complexes, recognizes complementary sequences and targets them for silencing. The PAZ domain is an RNA-binding module found in Argonaute and some Dicer proteins and its structure has been determined in the free state. Here, we report the 2.6 A crystal structure of the PAZ domain from human Argonaute eIF2c1 bound to both ends of a 9-mer siRNA-like duplex. In a sequence-independent manner, PAZ anchors the 2-nucleotide 3' overhang of the siRNA-like duplex within a highly conserved binding pocket, and secures the duplex by binding the 7-nucleotide phosphodiester backbone of the overhang-containing strand and capping the 5'-terminal residue of the complementary strand. On the basis of the structure and on binding assays, we propose that PAZ might serve as an siRNA-end-binding module for siRNA transfer in the RNA silencing pathway, and as an anchoring site for the 3' end of guide RNA within silencing effector complexes. Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain.,Ma JB, Ye K, Patel DJ Nature. 2004 May 20;429(6989):318-22. PMID:15152257[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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