University of Waterloo Biomedical Discussion Group - Dr. Xinhua JiExport this event to calendar

Wednesday, November 17, 2010 — 2:30 PM to 3:30 PM EST

Guest Speaker:  Dr. Xinhua Ji
(Chief, Biomolecular Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, U.S.A.)
Title of Presentation:  "Structure and functional cycle of essential GTPase Era:  Implications for ribosome biogenesis and antibiotic discovery"

[Host:  Dr. Qing-Bin Lu, Physics Dept.]
Refreshments will be available!

Abstract:  Era, composed of a GTPase domain and an RNA-binding KH domain, is essential for bacterial cell viability. It is required for the maturation of 16S ribosomal RNA (rRNA) and assembly of the 30S ribosomal subunit. Previously, we have shown that Era recognizes nine nucleotides (1531AUCACCUCC1539) near the 3' end of 16S rRNA and that this recognition stimulates the GTP-hydrolyzing activity of the protein (Proc. Natl. Acad. Sci. USA, 106:14843-14848, 2009). It is known that helix 45 (h45, nucleotides 1507-1528) and the 1530GAUCA1534 sequence are highly conserved in all three kingdoms of life. It is also known that a 1530GA1531 to AG mutation severely affects the viability of bacteria. However, whether Era interacts with G1530 and/or h45 and whether such interaction, if any, contribute to the stimulation of Era’s GTPase activity were not known. Recently, we have determined two more RNA structures that contain nucleotides 1506-1542 (RNA301) of 16S rRNA, one in complex with Era and a non-hydrolysable GTP-analog (GNP) and the other in complex with Era, GNP, and KsgA, a universally conserved methyltransferase that methylates two adjacent adenine bases in the tetraloop of h45. The structures show that Era does recognize G1530, and that Era also binds h45. However, GTPase assay experiments show that G1530 does not contribute to the stimulation of Era’s GTPase activity. Rather, A1531 and A1534 are most important for and h45 further contributes to the stimulation. Although G1530 does not contribute to the GTPase activity, its interaction with Era is essential for the protein to function, leading to the discovery of a new cold-sensitive phenotype of Era. Our data suggest a common mechanism for a highly conserved Ere function in all forms of life by recognizing the GAUCA sequence with a “twist” for non-eukaryotic Era proteins by also recognizing the CCUCC. Ere, present in nearly every bacterial species and is essential for both cell growth and division, is unique among all other known protein functions of bacteria. Inhibition of bacterial Era function will likely stop the synthesis of bacterial ribosome. Hence, Era is a potential target for developing novel antibiotics to fight the worldwide crisis of antibiotic resistance.

Location 
DC - William G. Davis Computer Research Centre
Room 1302
200 University Ave West

Waterloo, ON N2L 3G1
Canada

S M T W T F S
31
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
1
2
3
4
  1. 2022 (1)
  2. 2021 (40)
    1. December (8)
    2. November (3)
    3. October (3)
    4. September (4)
    5. August (5)
    6. July (3)
    7. June (1)
    8. May (2)
    9. April (4)
    10. March (3)
    11. February (1)
    12. January (3)
  3. 2020 (12)
    1. October (1)
    2. September (2)
    3. March (3)
    4. February (3)
    5. January (3)
  4. 2019 (38)
  5. 2018 (47)
  6. 2017 (53)
  7. 2016 (16)
  8. 2015 (49)
  9. 2014 (81)
  10. 2013 (88)
  11. 2012 (71)
  12. 2011 (156)
  13. 2010 (78)