Nucleotide-binding flexibility in ultrahigh-resolution structures of the SRP GTPase Ffh

Journal Article · Wed Oct 01 04:00:00 EDT 2008 · Acta Crystallographica. Section D: Biological Crystallography

DOI:https://doi.org/10.1107/S090744490802444X· OSTI ID:22347998

Ramirez, Ursula D.; Focia, Pamela J.

Crystal structures of the Ffh NG GTPase domain at < 1.24 Å resolution reveal multiple overlapping nucleotide binding modes. Two structures of the nucleotide-bound NG domain of Ffh, the GTPase subunit of the bacterial signal recognition particle (SRP), have been determined at ultrahigh resolution in similar crystal forms. One is GDP-bound and one is GMPPCP-bound. The asymmetric unit of each structure contains two protein monomers, each of which exhibits differences in nucleotide-binding conformation and occupancy. The GDP-bound Ffh NG exhibits two binding conformations in one monomer but not the other and the GMPPCP-bound protein exhibits full occupancy of the nucleotide in one monomer but only partial occupancy in the other. Thus, under the same solution conditions, each crystal reveals multiple binding states that suggest that even when nucleotide is bound its position in the Ffh NG active site is dynamic. Some differences in the positioning of the bound nucleotide may arise from differences in the crystal-packing environment and specific factors that have been identified include the relative positions of the N and G domains, small conformational changes in the P-loop, the positions of waters buried within the active site and shifts in the closing loop that packs against the guanine base. However, ‘loose’ binding may have biological significance in promoting facile nucleotide exchange and providing a mechanism for priming the SRP GTPase prior to its activation in its complex with the SRP receptor.

• OSTI ID: 22347998
• Journal Information: Acta Crystallographica. Section D: Biological Crystallography, Journal Name: Acta Crystallographica. Section D: Biological Crystallography Journal Issue: Pt 10 Vol. 64; ISSN ABCRE6; ISSN 0907-4449
• Country of Publication: Denmark
• Language: English

Related Subjects

75 CONDENSED MATTER PHYSICS
SUPERCONDUCTIVITY AND SUPERFLUIDITY
CONFORMATIONAL CHANGES
CRYSTAL STRUCTURE
CRYSTALS
ENVIRONMENT
FLEXIBILITY
IRON
MATHEMATICAL SOLUTIONS
MONOMERS
POSITIONING
RECEPTORS
RESOLUTION
SIGNALS
SOLUTIONS
STOWING