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Published on: November 1, 2011
The p12 domain is unstructured in a murine leukemia virus p12-CA(N) Gag construct
Sampson K Kyere1, Prem Raj B Joseph, Michael F Summers
1Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Maryland, Baltimore, Maryland, United States of America.
Abstract:
The Gag polyproteins of gammaretroviruses contain a conserved p12 domain between MA and CA that plays critical roles in virus assembly, reverse transcription and nuclear integration. Here we show using nuclear magnetic resonance, that p12 is unstructured in a Moloney murine leukemia virus (MMLV) Gag fragment that includes the N-terminal domain of CA (p12-CA(N)). Furthermore, no long range interactions were observed between the domains, as has been previously predicted. Flexibility appears to be a common feature of Gag "late" domains required for virus release during budding. Residues near the N-terminus of CA(N) that form a beta-hairpin in the mature CA protein are unfolded in p12-CA(N), consistent with proposals that hairpin formation helps trigger capsid assembly.
Insights
The p12 domain in gammaretroviruses Gag polyproteins is unstructured, lacking predicted long-range interactions. This flexibility in the p12-CA(N) fragment is crucial for viral assembly and release.
Area of Science:
- Virology
- Structural Biology
- Molecular Biology
Background:
- Gammaretroviruses Gag polyproteins are essential for viral replication.
- The p12 domain, located between MA and CA, is implicated in critical viral processes.
Purpose of the Study:
- To investigate the structural properties of the p12 domain within a Moloney murine leukemia virus (MMLV) Gag fragment.
- To determine the interactions between the p12 domain and the N-terminal domain of CA (CA(N)).
Main Methods:
- Nuclear magnetic resonance (NMR) spectroscopy was employed to analyze the structure of the p12-CA(N) fragment.
- Analysis focused on identifying long-range interactions and domain flexibility.
Main Results:
- The p12 domain within the p12-CA(N) fragment was found to be unstructured.
- No significant long-range interactions were detected between the p12 and CA(N) domains.
- Residues forming a beta-hairpin in mature CA were unfolded in the p12-CA(N) fragment.
Conclusions:
- The unstructured nature and flexibility of the p12 domain are key features for its function in virus assembly and release.
- Findings challenge previous predictions of long-range interactions, highlighting the dynamic nature of Gag polyproteins.
- The unfolded state of beta-hairpin forming residues supports models of capsid assembly triggered by hairpin formation.
