4a3t

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yeast regulatory particle proteasome assembly chaperone Hsm3yeast regulatory particle proteasome assembly chaperone Hsm3

Structural highlights

4a3t is a 2 chain structure with sequence from Saccharomyces cerevisiae W303. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HSM3_YEAST Involved in DNA mismatch repair in slow-growing cells. Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the 19S regulatory complex (RC).[1] [2] [3] [4] [5] [6] [7]

Publication Abstract from PubMed

The 26S proteasome, a molecular machine responsible for regulated protein degradation, consists of a proteolytic core particle (20S CP) associated with 19S regulatory particles (19S RPs) subdivided into base and lid subcomplexes. The assembly of 19S RP base subcomplex is mediated by multiple dedicated chaperones. Among these, Hsm3 is important for normal growth and directly targets the carboxyl-terminal (C-terminal) domain of Rpt1 of the Rpt1-Rpt2-Rpn1 assembly intermediate. Here, we report crystal structures of the yeast Hsm3 chaperone free and bound to the C-terminal domain of Rpt1. Unexpectedly, the structure of the complex suggests that within the Hsm3-Rpt1-Rpt2 module, Hsm3 also contacts Rpt2. We show that in both yeast and mammals, Hsm3 actually directly binds the AAA domain of Rpt2. The Hsm3 C-terminal region involved in this interaction is required in vivo for base assembly, although it is dispensable for binding Rpt1. Although Rpt1 and Rpt2 exhibit weak affinity for each other, Hsm3 unexpectedly acts as an essential matchmaker for the Rpt1-Rpt2-Rpn1 assembly by bridging both Rpt1 and Rpt2. In addition, we provide structural and biochemical evidence on how Hsm3/S5b may regulate the 19S RP association to the 20S CP proteasome. Our data point out the diverse functions of assembly chaperones.

Dual functions of the Hsm3 protein in chaperoning and scaffolding regulatory particle subunits during the proteasome assembly.,Barrault MB, Richet N, Godard C, Murciano B, Le Tallec B, Rousseau E, Legrand P, Charbonnier JB, Le Du MH, Guerois R, Ochsenbein F, Peyroche A Proc Natl Acad Sci U S A. 2012 Mar 29. PMID:22460800[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Fedorova IV, Gracheva LM, Kovaltzova SV, Evstuhina TA, Alekseev SY, Korolev VG. The yeast HSM3 gene acts in one of the mismatch repair pathways. Genetics. 1998 Mar;148(3):963-73. PMID:9539417
  2. ↑ Merker JD, Datta A, Kolodner RD, Petes TD. The yeast HSM3 gene is not involved in DNA mismatch repair in rapidly dividing cells. Genetics. 2000 Jan;154(1):491-3. PMID:10681182
  3. ↑ Fedorova IV, Kovaltzova SV, Korolev VG. The yeast HSM3 gene is involved in DNA mismatch repair in slowly dividing cells. Genetics. 2000 Jan;154(1):495-6. PMID:10681183
  4. ↑ Fedorova IV, Kovaltzova SV, Gracheva LM, Evstuhina TA, Korolev VG. Requirement of HSM3 gene for spontaneous mutagenesis in Saccharomyces cerevisiae. Mutat Res. 2004 Oct 4;554(1-2):67-75. PMID:15450405 doi:10.1016/j.mrfmmm.2004.03.003
  5. ↑ Funakoshi M, Tomko RJ Jr, Kobayashi H, Hochstrasser M. Multiple assembly chaperones govern biogenesis of the proteasome regulatory particle base. Cell. 2009 May 29;137(5):887-99. Epub 2009 May 14. PMID:19446322 doi:S0092-8674(09)00526-1
  6. ↑ Le Tallec B, Barrault MB, Guerois R, Carre T, Peyroche A. Hsm3/S5b participates in the assembly pathway of the 19S regulatory particle of the proteasome. Mol Cell. 2009 Feb 13;33(3):389-99. doi: 10.1016/j.molcel.2009.01.010. PMID:19217412 doi:10.1016/j.molcel.2009.01.010
  7. ↑ Roelofs J, Park S, Haas W, Tian G, McAllister FE, Huo Y, Lee BH, Zhang F, Shi Y, Gygi SP, Finley D. Chaperone-mediated pathway of proteasome regulatory particle assembly. Nature. 2009 Jun 11;459(7248):861-5. PMID:19412159 doi:nature08063
  8. ↑ Barrault MB, Richet N, Godard C, Murciano B, Le Tallec B, Rousseau E, Legrand P, Charbonnier JB, Le Du MH, Guerois R, Ochsenbein F, Peyroche A. Dual functions of the Hsm3 protein in chaperoning and scaffolding regulatory particle subunits during the proteasome assembly. Proc Natl Acad Sci U S A. 2012 Mar 29. PMID:22460800 doi:10.1073/pnas.1116538109

4a3t, resolution 2.10Å

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