TY - JOUR
T1 - Structures of Human Pumilio with Noncognate RNAs Reveal Molecular Mechanisms for Binding Promiscuity
AU - Gupta, Yogesh K.
AU - Nair, Deepak T.
AU - Wharton, Robin P.
AU - Aggarwal, Aneel K.
N1 - Funding Information:
We thank the staff at Advanced Photon Source (beamlines 17-ID and 17-BM) and at Brookhaven National Laboratory (beamlines X4C and X6A) for facilitating X-ray data collection. We thank J. Seetharaman for help with data collection. This work was supported by grant GM062947 from the National Institutes of Health (A.K.A. and R.P.W.). R.P.W. is an Investigator of the Howard Hughes Medical Institute.
PY - 2008/4/8
Y1 - 2008/4/8
N2 - Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycBreverse and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, in effect, acting as a "spacer." The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.
AB - Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycBreverse and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, in effect, acting as a "spacer." The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.
KW - RNA
UR - http://www.scopus.com/inward/record.url?scp=41449107841&partnerID=8YFLogxK
U2 - 10.1016/j.str.2008.01.006
DO - 10.1016/j.str.2008.01.006
M3 - Article
C2 - 18328718
AN - SCOPUS:41449107841
VL - 16
SP - 549
EP - 557
JO - Structure
JF - Structure
SN - 0969-2126
IS - 4
ER -