key: cord-015237-8cxfa8wf
authors: nan
title: Structure Watch
date: 2005
journal: Nat Rev Mol Cell Biol
DOI: 10.1038/nrm1780
sha: 
doc_id: 15237
cord_uid: 8cxfa8wf

nan

The solution structures of the four RNA-binding domains (RBDs) of polypyrimidine-tract-binding protein-1 (PTB1) in complex with RNA have now been solved by Oberstrass et al., leading to new models for the function of PTB1 as a repressor of alternative splicing. As an abundant eukaryotic RNAbinding protein, PTB1 is implicated in various aspects of RNA metabolism, but how it functions in these processes is not well understood. Oberstrass et al. used NMR to look at the structure of RBD1-4 in complex with a 5′-CUCUCU-3′ oligonucleotide, which is a common feature of intronic regulatory sequences.

Each RBD binds independently to one RNA molecule and recognizes a different consensus sequence within the oligonucleotide. The nucleotides interact with the flat β-sheet surface of each RBD but, unlike other RBD-RNA structures, the third β-strand is only weakly involved in RNA binding. Whereas most RBDs have four β-strands, RBD2 and RBD3 have a fifth β-strand, which allows these domains to interact with a larger nucleotide sequence.

Significantly, RBD3 and RBD4 interact extensively and have a fixed orientation such that their bound RNAs are antiparallel to each other and must be separated by a linker sequence. A single PTB1 molecule can therefore bring two distant pyrimidine tracts into close proximity and induce RNA looping -a feature that has led to the proposal of various models for the function of this protein in alternative splicing.

Structure of PTB bound to RNA: specific binding and implications for splicing regulation