Sm and Sm-like (Lsm) proteins are core components of the ribonucleoprotein complexes essential to key nucleic acid processing events within the eukaryotic cell nucleus (e.g. pre-mRNA splicing, mRNA degradation and histone processing). They assemble as poly-protein ring scaffolds that have the capacity to bind RNA substrates and other necessary protein factors. In viro, seven Lsm or Sm proteins form hetro-complexes, the exact components of which dictate the ultimate biological function. Thus, a heptameric assembly of Lsm [2+3+4+5+6+7+8] engages with and stabilises U6 snRNPs in the nucleus. Our group provided some of the first Lsm and Sm homo-heptameric ring structures of archaeal and eukaryotic origin (1,2). Here we report the first definition of a new organization of this family of proteins, found for a momomeric assembly of yeast Lsm3. The crystal structure revels a β-propeller ring of octomers organised via “head-to-head” stacking. Most importantly, the C-termini of some subunits are organised in additional beta sheet interactions with loop elements of neighbouring octomers. This provides some of the first understanding of the way in which Lsm proteins organise and recruit proteins to the ring scaffold. In an ongoing study to investigate inter-subunit interactions of Lsm assemblies, we have employed site-directed mutagenesis to identify key residues for thermal and folding stability. Chimaeras that introduce native-like interfaces into the Lsm3 homomeric assembly have enhanced thermal stability. The definition provided by our crystal structure of (Lsm3)₈ allows rationalisation of the key interfacial regions involved.
|Title of host publication||31st Lorne proteins conference, 2006|
|Place of Publication||Parkville, Vic.|
|Publisher||Lorne Proteins Organising Committee|
|Number of pages||1|
|Publication status||Published - 2006|
|Event||Lorne conference on protein structure and function (31st : 2006) - Lorne, Vic.|
Duration: 5 Feb 2006 → 9 Feb 2006
|Conference||Lorne conference on protein structure and function (31st : 2006)|
|Period||5/02/06 → 9/02/06|
Naidoo, N., Harrop, S. J., Curmi, P. M. G., & Mabbutt, B. C. (2006). 6's, 7's, and 8's: protein organization and recruitment in RNA-binding LSM complexes. In 31st Lorne proteins conference, 2006 (pp. 105). Parkville, Vic.: Lorne Proteins Organising Committee.