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PMID:24727835

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Citation

Gristick, HB, Rao, M, Chartron, JW, Rome, ME, Shan, SO and Clemons, WM Jr (2014) Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4. Nat. Struct. Mol. Biol. 21:437-42

Abstract

Correct localization of membrane proteins is essential to all cells. Chaperone cascades coordinate the capture and handover of substrate proteins from the ribosomes to the target membranes, yet the mechanistic and structural details of these processes remain unclear. Here we investigate the conserved GET pathway, in which the Get4-Get5 complex mediates the handover of tail-anchor (TA) substrates from the cochaperone Sgt2 to the Get3 ATPase, the central targeting factor. We present a crystal structure of a yeast Get3-Get4-Get5 complex in an ATP-bound state and show how Get4 primes Get3 by promoting the optimal configuration for substrate capture. Structure-guided biochemical analyses demonstrate that Get4-mediated regulation of ATP hydrolysis by Get3 is essential to efficient TA-protein targeting. Analogous regulation of other chaperones or targeting factors could provide a general mechanism for ensuring effective substrate capture during protein biogenesis.

Links

PubMed PMC4386898 Online version:10.1038/nsmb.2813

Keywords

Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/genetics; Adenosine Triphosphate/chemistry; Adenosine Triphosphate/metabolism; Amino Acid Sequence; Carrier Proteins/chemistry; Carrier Proteins/genetics; Crystallography, X-Ray; Gene Expression Regulation, Fungal; Guanine Nucleotide Exchange Factors/chemistry; Guanine Nucleotide Exchange Factors/genetics; Models, Molecular; Molecular Sequence Data; Protein Structure, Tertiary; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/genetics; Ubiquitin/chemistry; Ubiquitin/genetics

Significance

Annotations

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

YEAST:GET4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q12154

F

Seeded From UniProt

complete

YEAST:GET4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q12285

F

Seeded From UniProt

complete

YEAST:GET3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q12125

F

Seeded From UniProt

complete

YEAST:GET3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q12285

F

Seeded From UniProt

complete

YEAST:MDY2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q12125

F

Seeded From UniProt

complete

YEAST:MDY2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q12154

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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