LSm
This article may be too technical for most readers to understand.(August 2013) |
LSM domain | |||||||||
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CDD | cd00600 | ||||||||
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In
The Sm proteins were first discovered as
Proteins with similar structures are grouped into a hierarchy of protein families, superfamilies, and folds. The LSm protein structure is an example of a small
Alternate terms for LSm family are LSm fold and Sm-like fold, and alternate capitalization styles such as lsm, LSM, and Lsm are common and equally acceptable.
History
Discovery of the Smith antigen
The story of the discovery of the first LSm proteins begins with a young woman, Stephanie Smith, who was diagnosed in 1959 with systemic lupus erythematosus (SLE), eventually succumbing to complications of the disease in 1969 at the age of 22.[1] During this period, she was treated at New York's Rockefeller University Hospital, under the care of Dr. Henry Kunkel and Dr. Eng Tan. As those with an autoimmune disease, SLE patients produce antibodies to antigens in their cells' nuclei, most frequently to their own DNA. However, Kunkel and Tan found in 1966 that Smith produced antibodies to a set of nuclear proteins, which they named the 'smith antigen' (Sm Ag).[2] About 30% of SLE patients produce antibodies to these proteins, as opposed to double stranded DNA. This discovery improved diagnostic testing for SLE, but the nature and function of this antigen was unknown.
Sm proteins, snRNPs, the spliceosome and messenger RNA splicing
Research continued during the 1970s and early 1980s. The smith antigen was found to be a complex of ribonucleic acid (
Discovery of proteins similar to the Sm proteins
The snRNA U6 (unlike U1, U2, U4 and U5) does not associate with the Sm proteins, even though the U6 snRNP is a central component in the
Discovery of the LSm fold
Around 1995, comparisons between the various LSm
Structure
Secondary
The
Tertiary
SCOP simply classifies the LSm structure as the Sm-like fold, one of 149 different Beta Protein folds, without any intermediate groupings. The LSm beta sheet is sharply bent and described as a Roll architecture in CATH (one of 20 different beta protein architectures in CATH). One of the beta strands (β5 in LSm) crosses the open edge of the roll to form a small SH3 type barrel topology (one of 33 beta roll topologies in CATH). CATH lists 23 homologous superfamilies with an SH3 type barrel topology, one of which is the LSm structure (RNA Binding Protein in the CATH system). SCOP continues its structural classification after Fold to Superfamily, Family and Domain, while CATH continues to Sequence Family, but these divisions are more appropriately described in the "Evolution and phylogeny" section.
The SH3-type barrel
Quaternary
LSm proteins typically assemble into a LSm ring, a six or seven member
RNA oligonucleotide binding
LSm rings form
Functions
The various kinds of LSm rings function as scaffolds or
Sm ring
The Sm ring is found in the
Lsm2-8 ring
The two Lsm2-8 snRNPs (U6 and
Sm10/Sm11 ring
A second type of Sm ring exists where
Like the Sm ring, it is assembled in the cytoplasm onto the U7 snRNA by a specialized SMN complex.Lsm1-7 ring
A second type of Lsm ring is the Lsm1-7 ring, which has the same structure as the Lsm2-8 ring except that LSm1 replaces LSm8. In contrast to the Lsm2-8 ring, the Lsm1-7 ring localizes in the
Gemin6 and Gemin7
The SMN complex (described under "Biogenesis of snRNPs") is composed of the SMN protein and Gemin2-8. Two of these, Gemin 6 and Gemin7 have been discovered to have the LSm structure, and to form a heterodimer. These may have a
LSm12-16 and other multi-domain LSm proteins
The LSm12-16 proteins have been described very recently. These are two-domain proteins with a
Archaeal Sm rings
Two LSm proteins are found in a second
Bacterial LSm rings
Several LSm proteins have been reported in the third
Evolution and phylogeny
LSm
Homomeric LSm rings in bacteria and archaea
Based on structure, the known LSm proteins divide into a group consisting of the bacterial LSm proteins (Hfq, YlxS and MscS) and a second group of all other LSm proteins, in accordance with the most recently published phylogenetic trees.[26] The three archaeal LSm proteins (Sm1, Sm2 and Sm3) also cluster as a group, distinct from the eukaryote LSm proteins. Both the bacterial and archaeal LSm proteins polymerize to homomeric rings, which is the ancestral condition.
Heteromeric LSm rings in eukaryotes
A series of gene duplications of a single eukaryote LSm gene resulted in most (if not all) of the known eukaryote LSm genes. Each of the seven Sm proteins has greater
Biogenesis of snRNPs
Small nuclear ribonucleoproteins (snRNPs) assemble in a tightly orchestrated and regulated process that involves both the cell nucleus and cytoplasm.[27]
References
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- ^ National Center for Biotechnology Information Structure Database PDB codes 1B34, 1D3B, 1I5L, 1KQ2, 1N9S, 1IB8.
- PMID 16051491.
- PMID 11226169.
- S2CID 4414530.
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- ^
Chari A, Golas MM, Klingenhäger M, Neuenkirchen N, Sander B, Englbrecht C, Sickmann A, Stark H, Fischer U (2008-10-31). "An Assembly Chaperone Collaborates with the SMN Complex to Generate Spliceosomal SnRNPs". Cell. 135 (3): 497–509. S2CID 119444.
- S2CID 37187215.
- ^ PMID 34362892.
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