Sandbox 502: Difference between revisions

=Introduction=

Sm-like ([http://en.wikipedia.org/wiki/LSm Lsm]) proteins most closely resemble Sm proteins, both of which are found in the three domains of life <ref name ="wu">PMID:22615807</ref>.  Sm proteins play a large role in [http://en.wikipedia.org/wiki/Spliceosome spliceosome] biogenesis through mediating U1, U2, U4, U5, and U6 [http://en.wikipedia.org/wiki/SnRNP snRNP assembly]<ref name ="he">PMID:10801455</ref>.  The <scene name='Sandbox_502/U1_sm_ring/2'>Sm ring</scene> of proteins can be broken down into seven specific proteins (SmB, SmD1, SmD2, SmD3, SmE, SmF, and SmG in humans) all of which share a conserved Sm motif which is also found in the Lsm proteins<ref name ="he"/><ref name ="naidoo"/>. Eukaryotes have 16 or more Lsm proteins encoded in their genome, in contrast archaeal species have only one to three <ref name ="naidoo">PMID:18329667</ref>.  A total of nine specific Lsm proteins are found in yeast (Lsm1-Lsm9).  The Lsm proteins 2-7 most closely resemble Sm proteins D1-G, where Lsm 1 and 8 most closely resemble the SmB proteins <ref name ="he"/>.  Lsm9 does not appear to resemble any of the Sm proteins, although there have been some related structures found in the archaeal genome <ref name ="he"/>.  Several studies have shown that the Sm proteins form into seven membered rings which bind to the Sm binding site, a U rich sequence found in all but U6 snRNA<ref name ="he"/>.  Lsm proteins can form homomeric rings of heptamers, hexamers, or octamers<ref name ="wu"/>.  In addition they have been found to predominately associate into three complexes: Lsm2-8, Lsm1-7, and Lsm2-7 <ref name ="wu"/>.  The exact functionality of these complexes is in either [http://en.wikipedia.org/wiki/RNA_splicing pre-mRNA splicing], [http://en.wikipedia.org/wiki/Messenger_RNA#Degradation mRNA decay] or other roles, and is dictated by their composition, structure, and cellular location <ref name ="wu"/><ref name ="he"/>.  

=Structure of Lsm proteins=

Sm and Lsm proteins both exhibit the Sm motif, which consist of an N-terminal [http://en.wikipedia.org/wiki/Alpha_helix α-helix] proceeded by a twisted five stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet] <ref name ="wu"/><ref name ="naidoo"/>).  Loop L4, located between stands β3 and β4 of the β sheet, varies between 3 to 30 residues in length across the different Lsm proteins <ref name ="naidoo"/>.  The β-sheet encloses a set of hydrophobic residues <ref name ="naidoo"/>.  When the Lsm ring is assembled the hydrophobic region spreads into the now adjacent Lsm protein monomers <ref name ="naidoo"/>.  When assembled into the ring between each subunit there are hydrogen bonds formed between β4 of one subunit and β5 of the neighboring subunit <ref name ="naidoo"/>.  These interactions provided the Lsm ring with enough contacts to make a very stable structure <ref name ="naidoo"/>.  There are two sides to the ring, the helix face and the loop face, found on opposite sides of the ring <ref name ="wu"/>.  It has been postulated that a U-rich RNA may bind to the inner portion of the helix face, and take part in hydrogen bonding interactions with residues located on loops 3 and 5, as well as potentially pass through the pore itself <ref name ="naidoo"/>.   

===ScLsm3===

The ScLsm3 crystal structure takes the form of a ring composed of eight monomeric subunits.  Each monomer contains the Sm motif containing the N-terminal α-helix (pro4-leu10) and the curved β-sheet (Glu14-Ser77).  The stands β3 and β4 are long, which causes loop L4 residues to stick out and twist away from the main body of the ring.  The only other Sm/Lsm protein to exhibit this is the human Sm protein SmB.  Between each of the subunits there are hydrogen interactions between the C-terminal region of β4 and the neighboring β5.  In addition, there are hydrophobic residues buried at this interface, which include Phe67, Ile68, Thr74, and Ile76.  The overall ring structure is approximately 75Å wide, 50Å thick.  The pore is approximately 20Å at the helix face and 25Å at the loop face.  These measurements are greater than those of six or seven membered Lsm rings <ref name ="naidoo"/>.

===SpLsm3===

As in ScLsm3, SpLsm3 exhibits the sm motif containing an N-terminal α-helix (residues 10-17) and a curved β-sheet (residues 19-89).  However rather than forming an octomeric ring structure it formed a heptameric ring structure in crystallization experiments.  SpLsm3 monomers interact through the same β4-β5 pairing as in ScLsm3.  The overall ring is 61.5Å wide, 31Å thick, where the pore is approximately 20.7Å wide.  In this crystal structure loop four is distorted <ref name ="wu"/>.  

The Lsm4 crystal structure contains a trimer of the Lsm4 monomers.  It contains the Sm motif consisting of an α-helix (distorted) and a β-sheet formed by five antiparallel stands (residues 14-70)<ref name ="wu"/>.

==Lsm 5/6/7==

A 2.5Å resolution structure of Lsm5, Lsm6 and Lsm7 has been determined where the crystal contains two hexameric Lsm657-657 rings.  Lsm5 is located between Lsm6 and Lsm7 which analogous to their Sm counters parts.  In the hexameric ring each subunit interacts in the same manner as the other Lsm proteins (ie through the β4 stand of one subunit to the β5 strand of the other) to form a continuous β-sheet through the whole ring.  Each of the Lsm proteins exhibits the Sm motif with very small differences seen between them <ref name ="mund">PMID:22001694</ref>.  

=Additional Resources=

=References=

<References/>