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PMID:22124326

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Citation

Suloway, CJ, Rome, ME and Clemons, WM Jr (2012) Tail-anchor targeting by a Get3 tetramer: the structure of an archaeal homologue. EMBO J. 31:707-19

Abstract

Efficient delivery of membrane proteins is a critical cellular process. The recently elucidated GET (Guided Entry of TA proteins) pathway is responsible for the targeted delivery of tail-anchored (TA) membrane proteins to the endoplasmic reticulum. The central player is the ATPase Get3, which in its free form exists as a dimer. Biochemical evidence suggests a role for a tetramer of Get3. Here, we present the first crystal structure of an archaeal Get3 homologue that exists as a tetramer and is capable of TA protein binding. The tetramer generates a hydrophobic chamber that we propose binds the TA protein. We use small-angle X-ray scattering to provide the first structural information of a fungal Get3/TA protein complex showing that the overall molecular envelope is consistent with the archaeal tetramer structure. Moreover, we show that this fungal tetramer complex is capable of TA insertion. This allows us to suggest a model where a tetramer of Get3 sequesters a TA protein during targeting to the membrane.

Links

PubMed PMC3273380 Online version:10.1038/emboj.2011.433

Keywords

Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/metabolism; Amino Acid Sequence; Archaea/chemistry; Archaea/metabolism; Guanine Nucleotide Exchange Factors/chemistry; Guanine Nucleotide Exchange Factors/metabolism; Models, Molecular; Molecular Sequence Data; Protein Binding; Protein Conformation; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

METJA:ARSA

enables

GO:0042802: identical protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q58542

F

Seeded From UniProt

complete

YEAST:GET3

enables

GO:0042802: identical protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q12154

F

Seeded From UniProt

complete

Notes

See also

References

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