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Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
Published on: March 11, 2021
Structural basis of Fic-mediated adenylylation
Junyu Xiao1, Carolyn A Worby, Seema Mattoo
1Department of Pharmacology, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California, USA.
Nature Structural & Molecular Biology
|July 13, 2010
Summary
The structure of a bacterial protein (IbpAFic2) bound to Cdc42 reveals how it modifies Rho GTPases. This provides the first structural insight into adenylylation, a key post-translational modification.
Area of Science:
- Biochemistry
- Structural Biology
- Microbiology
Background:
- The Fic (Filamin, Ion channel, and修为) family comprises over 2,700 adenylyltransferases.
- IbpA from Histophilus somni uses its Fic domains to modify Rho GTPases, aiding bacterial pathogenesis.
Purpose of the Study:
- To determine the structure of the IbpA Fic domain 2 (IbpAFic2) in complex with its substrate Cdc42.
- To elucidate the mechanism of adenylylation of Rho GTPases by Fic proteins.
Main Methods:
- X-ray crystallography to obtain the IbpAFic2-Cdc42 complex structure.
- Site-directed mutagenesis to assess the functional importance of the protein-protein interface.
Main Results:
- The structure reveals IbpAFic2 binding to Cdc42 in a GDI-bound-like conformation.
- The switch1 tyrosine of Cdc42 is adenylylated within the complex, offering the first structural view of this modification.
- Mutations at the interface reduce adenylylation and cytotoxicity.
Conclusions:
- The findings provide a structural basis for understanding Fic-mediated adenylylation.
- The conserved nucleotide-binding mechanism suggests a common catalytic strategy for Fic enzymes.
- This work offers insights into bacterial subversion of host defenses.
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