Hamm Lab

Education:
Ph.D. Biotechnology Institute, University of Ankara, Turkey, 2009
MSc. School of Medicine, Medical Biology Department, University of Ankara, Turkey. 2003

Research Interests: 
Heterotrimeric G proteins are one of the most important signal transducing molecules in the cells. They trigger different intracellular signaling cascades in response to the activated GPCRs. Ligand activation of GPCRs leads to G protein binding and catalyzes GDP release from the G protein a subunit. Once GDP is released, a stable, high-affinity complex between the activated receptor and nucleotide free G protein is formed. Binding of GTP to Ga destabilizes this complex and results in dissociation of receptor, GTP-bound Ga and Gbg. Both Gaand Gbg subunits then trigger downstream signaling cascades. After GTP is hydrolyzed to GDP, the Ga subunit reassociates with Gbg, thus completing the cycle.

The guanine nucleotide-binding pocket of the Ga subunit is ~25 Å away from the receptor contact sites. Thus, the receptor must induce a conformational change in the G protein to cause GDP release over this distance. Different studies proposed the potential receptor-catalyzed GDP release mechanisms. Our lab identified that activated rhodopsin induces a rotation and translation of the Ga a5 helix and for receptor-mediated GTP-GDP exchange to occur, the GTPase and helical domains must open up. Although the position of the helical domain is critical for GDP release, the mechanisms of the trigger of this large conformational change are still unknown. Our major focus is to understand the molecular and mechanistic basis of G protein activation by an activated receptor.

Publications:

Functional stability of rhodopsin in a bicelle system: evaluating G protein activation by rhodopsin in bicelles.  Kaya AI, Iverson TM, Hamm HE.  Methods Mol Biol. 2015;1271:67-76.

A conserved phenylalanine as a relay between the α5 helix and the GDP binding region of heterotrimeric Gi protein α subunit.  Kaya AI, Lokits AD, Gilbert JA, Iverson TM, Meiler J, Hamm HE.  J Biol Chem. 2014 Aug 29;289(35):24475-87.

Energetic analysis of the rhodopsin-G-protein complex links the α5 helix to GDP release.  Alexander NS, Preininger AM, Kaya AI, Stein RA, Hamm HE, Meiler J.  Nat Struct Mol Biol. 2014 Jan;21(1):56-63.

Linking receptor activation to changes in Sw I and II of Gα proteins.  Hamm HE, Kaya AI, Gilbert JA 3rd, Preininger AM.  J Struct Biol. 2013 Oct;184(1):63-74.

Preininger A.M., Kaya A.I., Gilbert J.A. 3rd, Busenlehner L.S., Armstrong R.N., Hamm H.E. Myristoylation exerts direct and allosteric effects on Gα conformation and dynamics in solution. Biochemistry. 2012, 51(9): 1911-24.

Kaya A.I., Onaran H.O., Ozcan G, Ambrosio C, Costa T, Balh S, Ugur O. Cell Contact-Dependent Functional Selectivity of β2-Adrenergic Receptor Ligands in Stimulating cAMP Accumulation and Extracellular Signal-Regulated Kinase (ERK) Phosphorylation. J. Biol. Chem. 2012, 287: 6362-74.

Thaker T.M., Kaya A.I., Preininger A.M., Hamm H.E., Iverson T.M. Allosteric mechanisms of G protein-Coupled Receptor signaling: a structural perspective. Methods Mol Biol. 2012,796:133-74.

Kaya A.I, Ugur O, Altuntas O, Sayar K, Onaran H.O. Long and short distance movements of β(2)-adrenoceptor in cell membrane assessed by photoconvertible fluorescent protein dendra2-β(2)-adrenoceptor fusion. Biochim Biophys Acta. 2011, 1813(8):1511-24

Van Eps N., Preininger A.M., Alexander N., Kaya A.I, Meier S., Meiler J., Hamm H.E., Hubbell W.L. Interaction of a G protein with an activated receptor opens the interdomain interface in the alpha subunit. PNAS. 2011, 108(23);9420-9424

Kaya A.I, Thaker T.M., Preininger A.M., Iverson T.M., Hamm H.E. Coupling Efficiency of Rhodopsin and Transducin in Bicelles. Biochemistry. 2011,  15(50); 3193-3203

Oner S.S., Kaya A.I., Onaran H.O., Ozcan G., Ugur O. β2-Adrenoceptor, Gs and adenylate cyclase coupling in purified detergent-resistant, low-density membrane fractions. Eur J Pharmacol. 2010, 630: 42-52