Crystal structures of two forms of the Acanthamoeba polyphaga mimivirus Rab GTPase

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Acanthamoeba polyphaga mimivirus (APMV) is a giant virus with a large genome.
• Rab GTPases are key regulators of membrane trafficking, previously thought to be exclusive to eukaryotes.
• The APMV genome contains a gene encoding a Rab GTPase homologue.

Purpose of the Study:

• To determine the high-resolution crystal structures of the APMV Rab GTPase in its GDP- and GTP-bound forms.
• To elucidate the atomic-level mechanism of the inactive-active conformational change upon nucleotide exchange.
• To compare the structure of APMV Rab with mammalian Rab homologues and identify unique features.

Main Methods:

• High-resolution X-ray crystallography
• Structural comparison of APMV Rab with mammalian Rab proteins

Main Results:

• The crystal structures of both GDP- and GTP-bound APMV Rab GTPase were determined at high resolution.
• Structural comparison revealed significant similarity to human Rab5, as predicted.
• Unique structural features were identified in APMV Rab, including a phenylalanine residue involved in guanine base stabilization, differentiating it from mammalian homologues.

Conclusions:

• APMV Rab GTPase shares structural similarities with eukaryotic Rab proteins but possesses unique characteristics.
• The study provides atomic-level insights into the conformational changes associated with nucleotide binding and exchange in APMV Rab.
• The findings expand our understanding of the distribution and evolution of essential cellular machinery in giant viruses.