4a20

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Crystal structure of the Ubl domain of Mdy2 (Get5) at 1.78ACrystal structure of the Ubl domain of Mdy2 (Get5) at 1.78A

Structural highlights

4a20 is a 1 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.78Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MDY2_YEAST Required for efficient mating. Involved in the production of alpha-factor, the KAR9 and TUB1 location to the shmoo tip and nuclear migration into pheromone-induced shmoos.[1] [2]

Publication Abstract from PubMed

Small, glutamine-rich, tetratricopeptide repeat protein 2 (Sgt2) is the first known port of call for many newly synthesized tail-anchored (TA) proteins released from the ribosome and destined for the GET (Guided Entry of TA proteins) pathway. This leads them to the residential membrane of the endoplasmic reticulum via an alternative to the cotranslational, signal recognition particle-dependent mechanism that their topology denies them. In yeast, the first stage of the GET pathway involves Sgt2 passing TA proteins on to the Get4/Get5 complex through a direct interaction between the N-terminal (NT) domain of Sgt2 and the ubiquitin-like (UBL) domain of Get5. Here we characterize this interaction at a molecular level by solving both a solution structure of Sgt2_NT, which adopts a unique helical fold, and a crystal structure of the Get5_UBL. Furthermore, using reciprocal chemical shift perturbation data and experimental restraints, we solve a structure of the Sgt2_NT/Get5_UBL complex, validate it via site-directed mutagenesis, and empirically determine its stoichiometry using relaxation experiments and isothermal titration calorimetry. Taken together, these data provide detailed structural information about the interaction between two key players in the coordinated delivery of TA protein substrates into the GET pathway.

Structure of the Sgt2/Get5 complex provides insights into GET-mediated targeting of tail-anchored membrane proteins.,Simon AC, Simpson PJ, Goldstone RM, Krysztofinska EM, Murray JW, High S, Isaacson RL Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1327-32. doi:, 10.1073/pnas.1207518110. Epub 2013 Jan 7. PMID:23297211[3]

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

References

  1. Iwanejko L, Smith KN, Loeillet S, Nicolas A, Fabre F. Disruption and functional analysis of six ORFs on chromosome XV: YOL117w, YOL115w ( TRF4), YOL114c, YOL112w ( MSB4), YOL111c and YOL072w. Yeast. 1999 Oct;15(14):1529-39. PMID:10514570 doi:<1529::AID-YEA457>3.0.CO;2-Y 10.1002/(SICI)1097-0061(199910)15:14<1529::AID-YEA457>3.0.CO;2-Y
  2. Hu Z, Potthoff B, Hollenberg CP, Ramezani-Rad M. Mdy2, a ubiquitin-like (UBL)-domain protein, is required for efficient mating in Saccharomyces cerevisiae. J Cell Sci. 2006 Jan 15;119(Pt 2):326-38. Epub 2006 Jan 3. PMID:16390866 doi:jcs.02754
  3. Simon AC, Simpson PJ, Goldstone RM, Krysztofinska EM, Murray JW, High S, Isaacson RL. Structure of the Sgt2/Get5 complex provides insights into GET-mediated targeting of tail-anchored membrane proteins. Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1327-32. doi:, 10.1073/pnas.1207518110. Epub 2013 Jan 7. PMID:23297211 doi:http://dx.doi.org/10.1073/pnas.1207518110

4a20, resolution 1.78Å

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