6's, 7's, and 8's

protein organization and recruitment in RNA-binding LSM complexes

N. Naidoo, S. J. Harrop, P. M. G. Curmi, B. C. Mabbutt

Research output: Chapter in Book/Report/Conference proceedingOther chapter contribution

Abstract

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.
Original languageEnglish
Title of host publication31st Lorne proteins conference, 2006
Place of PublicationParkville, Vic.
PublisherLorne Proteins Organising Committee
Pages105
Number of pages1
ISBN (Print)9781604237504
Publication statusPublished - 2006
EventLorne conference on protein structure and function (31st : 2006) - Lorne, Vic.
Duration: 5 Feb 20069 Feb 2006

Conference

ConferenceLorne conference on protein structure and function (31st : 2006)
CityLorne, Vic.
Period5/02/069/02/06

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