4zrl | pdb_00004zrl
Structure of the non canonical Poly(A) polymerase complex GLD-2 - GLD-3
Structural highlights
Function[GLD2_CAEEL] Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail. Acts as a regulator of mitosis/meiosis required for progression through meiotic prophase during oogenesis and spermatogenesis and for promotion of the entry into meiosis from the mitotic cell cycle. May act by regulating and activating gld-1 mRNA activity in germline.[1] [2] [3] [4] [5] [6] [7] [GLD3_CAEEL] Required maternally for germline survival and embryogenesis. Forms a complex with gls-1 which promotes the oogenic cell fate by freeing the translational repressor fbf to repress sperm promoting factors. Promotes maturation of primary spermatocytes to mature sperm. Required during hermaphrodite development to promote sperm fate, which is critical for determining the normal number of sperm. Promotion of sperm fate is at the expense of oogenesis, possibly through the negative regulation of fbf. Required during male development for the continued production of sperm and inhibition of oogenesis. Together with gld-2, promotes the transition from mitosis to meiosis.[8] [9] [10] Publication Abstract from PubMedThe Caenorhabditis elegans germ-line development defective (GLD)-2-GLD-3 complex up-regulates the expression of genes required for meiotic progression. GLD-2-GLD-3 acts by extending the short poly(A) tail of germ-line-specific mRNAs, switching them from a dormant state into a translationally active state. GLD-2 is a cytoplasmic noncanonical poly(A) polymerase that lacks the RNA-binding domain typical of the canonical nuclear poly(A)-polymerase Pap1. The activity of C. elegans GLD-2 in vivo and in vitro depends on its association with the multi-K homology (KH) domain-containing protein, GLD-3, a homolog of Bicaudal-C. We have identified a minimal polyadenylation complex that includes the conserved nucleotidyl-transferase core of GLD-2 and the N-terminal domain of GLD-3, and determined its structure at 2.3-A resolution. The structure shows that the N-terminal domain of GLD-3 does not fold into the predicted KH domain but wraps around the catalytic domain of GLD-2. The picture that emerges from the structural and biochemical data are that GLD-3 activates GLD-2 both indirectly by stabilizing the enzyme and directly by contributing positively charged residues near the RNA-binding cleft. The RNA-binding cleft of GLD-2 has distinct structural features compared with the poly(A)-polymerases Pap1 and Trf4. Consistently, GLD-2 has distinct biochemical properties: It displays unusual specificity in vitro for single-stranded RNAs with at least one adenosine at the 3' end. GLD-2 thus appears to have evolved specialized nucleotidyl-transferase properties that match the 3' end features of dormant cytoplasmic mRNAs. Structural basis for the activation of the C. elegans noncanonical cytoplasmic poly(A)-polymerase GLD-2 by GLD-3.,Nakel K, Bonneau F, Eckmann CR, Conti E Proc Natl Acad Sci U S A. 2015 Jun 29. pii: 201504648. PMID:26124149[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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