ABSTRACT
Heterotrimeric guanine nucleotide-binding proteins (G proteins) are composed of α, ß, and γ subunits, and Gα has a GDP/GTP-binding pocket. When a guanine nucleotide exchange factor (GEF) interacts with Gα, GDP is released, and GTP interacts to Gα. The GTP-bound activated Gα dissociates from GEF and Gßγ, mediating the induction of various intracellular signaling pathways. Depending on the sequence similarity and cellular function, Gα subunits are subcategorized into four subfamilies: Gαi/o, Gαs, Gαq/11, and Gα12/13. Although the Gαi/o subtype family proteins, Gαi3 and GαoA, share similar sequences and functions, they differ in their GDP/GTP turnover profiles, with GαoA possessing faster rates than Gαi3. The structural factors responsible for these differences remain unknown. In this study, we employed hydrogen/deuterium exchange mass spectrometry and mutational studies to investigate the factors responsible for these functional differences. The Gα subunit consists of a Ras-like domain (RD) and an α-helical domain (AHD). The RD has GTPase activity and receptor-binding and effector-binding regions; however, the function of the AHD has not yet been extensively studied. In this study, the chimeric construct containing the RD of Gαi3 and the AHD of GαoA showed a GDP/GTP turnover profile similar to that of GαoA, suggesting that the AHD is the major regulator of the GDP/GTP turnover profile. Additionally, site-directed mutagenesis revealed the importance of the N-terminal part of αA and αA/αB loops in the AHD for the GDP/GTP exchange. These results suggest that the AHD regulates the nucleotide exchange rate within the Gα subfamily.
Subject(s)
GTP-Binding Protein alpha Subunits, Gi-Go , Heterotrimeric GTP-Binding Proteins , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolism , Guanosine Diphosphate/metabolism , Guanosine Triphosphate/metabolism , Heterotrimeric GTP-Binding Proteins/metabolismABSTRACT
The maxillary artery (MA) passes over the lateral pterygoid muscle in the infratemporal fossa and enters the pterygopalatine fossa through the pterygomaxillary fissure. Refractory epistaxis is managed by ligation of the sphenopalatine artery via a transmaxillary-transantral approach; there is considerable risk of complications associated with such invasive surgical approaches. The aim of this study was to describe the gross anatomy and variations therein of the MA and its branches at the pterygopalatine fossa. One hundred hemifaces of embalmed Korean adult cadavers were dissected to establish the precise course of the MA and its branching patterns. The average thickness of the posterior wall of the maxillary sinus was 0.8 mm, but varied over a wide range from 0.2 to 3.6 mm. We classified the third part of the MA into 3 morphological categories: looped (61%), bifurcated (19%), and straight (18%). Two cases could not be classified into any of these 3 categories. The pattern of the bifurcation between the sphenopalatine and descending palatine arteries was classified into 4 types: Y (19%), intermediate (36%), M (17%), and T (28%). The posterior wall of the maxillary sinus was divided into 9 sections. The branching areas of the sphenopalatine and descending palatine arteries were most frequently (62% of cases) located at the top of the medial partition and at the middle of the medial partition (30% of cases).