The Faculty

Focus

Adhesion-type G protein coupled receptors, GAIN domains, brain functions and diseases

Biography

University of Chicago, Assistant Professor, 2013-

Stanford University, Postdoctoral fellow, 2006-2013

University of Texas Southwestern Medical Center at Dallas, Ph.D. in Molecular Biophysics, 2000-2006

Bilkent University, B.Sc. in Molecular Biology and Genetics, 1995-1999

Accolades

Life Sciences Research Foundation (LSRF), Post-doctoral Fellowship (sponsored by HHMI), 2007-2010

Chancellor’s Distinguished Fellowship, University of California, Riverside, Graduate Student Fellowship, 1999-2000

St. Mary’s School of Medicine, UK, Summer Undergraduate Research Fellow, Full Scholarship, 1998 and 1999

B.S., Bilkent University, Full Scholarship, 1995-1999

TUBITAK, Young Scientist Scholarship, 1995-1996

Courses Taught

Structure and Function of Membrane Proteins (together with Eduardo Perozo)

BPHYS Student

Gabriel Salzman, PhD

Research Interests

The G-protein coupled receptor (GPCR) superfamily is the largest group of membrane proteins and the most commonly targeted group of molecules for the treatment of human diseases. Adhesion-type GPCRs are a newly discovered GPCR family with emerging roles in multiple brain functions and disorders such as brain development, synapse maturation/elimination, bilateral frontoparietal polymicrogyria (BFPP, a neurodevelopmental disorder), attention-deficit hyperactivity disorder, and cancers of the brain. The goal of our laboratory is to understand the mechanism by which adhesion GPCRs function in the brain, and to decipher the role of the newly discovered GPCR Autoproteolysis Inducing (GAIN) domain in their function. We aim to identify ligands for adhesion GPCRs and to reveal the molecular mechanisms by which adhesion GPCRs recognize their ligands through their GAIN domains and transmembrane helices. We also aim to shed light on how the extracellular GAIN domain and the membrane-embedded transmembrane helices act together to regulate receptor activity. We explore these questions from a biochemical/biophysical point of view through protein biochemistry, x-ray crystallography, and biophysical techniques. We complement our molecular studies with functional studies to understand the structure/function relationship and put our findings at the molecular level in the context of the physiological receptor activity. Our results will have an enormous impact scientifically by elucidating how cellular adhesion couples to intracellular signaling in multicellular organisms, a key phenomenon that is disrupted in many human diseases, and, translationally, through targeted drug design to treat brain diseases caused by malfunctioning adhesion GPCRs.

Selected Publications

Specific and direct modulation of the interaction between adhesion GPCR GPR56/ADGRG1 and tissue transglutaminase 2 using synthetic ligands
Salzman GS, Zhang S, Fernandez CG, Araç D, Koide S.
Sci Rep. 2020 Oct 9;10(1):16912. doi: 10.1038/s41598-020-74044-6. PMID: 33037308

Alternative splicing controls teneurin-latrophilin interaction and synapse specificity by a shape-shifting mechanism
Li J, Xie Y, Cornelius S, Jiang X, Sando R, Kordon SP, Pan M, Leon K, Südhof TC, Zhao M, Araç D.
Nat Commun. 2020 May 1;11(1):2140. doi: 10.1038/s41467-020-16029-7. PMID: 32358586 

Structural basis for adhesion G protein-coupled receptor Gpr126 function
Leon K, Cunningham RL, Riback JA, Feldman E, Li J, Sosnick TR, Zhao M, Monk KR, Araç D.
Nat Commun. 2020 Jan 10;11(1):194. doi: 10.1038/s41467-019-14040-1. PMID: 31924782

Teneurin Structure: Splice Variants of a Bacterial Toxin Homolog Specifies Synaptic Connections
Araç D, Li J.
Front Neurosci. 2019 Aug 7;13:838. doi: 10.3389/fnins.2019.00838. eCollection 2019. PMID: 31440135  

Teneurins and latrophilins: two giants meet at the synapse
Araç D, Li J.
Curr Opin Struct Biol. 2019 Feb;54:141-151. doi: 10.1016/j.sbi.2019.01.028. Epub 2019 Apr 2.PMID: 30952063  

A Comprehensive Mutagenesis Screen of the Adhesion GPCR Latrophilin-1/ADGRL1
Nazarko O, Kibrom A, Winkler J, Leon K, Stoveken H, Salzman G, Merdas K, Lu Y, Narkhede P, Tall G, Prömel S, Araç D.
iScience. 2018 May 25;3:264-278. doi: 10.1016/j.isci.2018.04.019. Epub 2018 Apr 30. PMID: 30428326 

A new MR-SAD algorithm for the automatic building of protein models from low-resolution X-ray data and a poor starting model
Skubák P, Araç D, Bowler MW, Correia AR, Hoelz A, Larsen S, Leonard GA, McCarthy AA, McSweeney S, Mueller-Dieckmann C, Otten H, Salzman G, Pannu NS. NS.IUCrJ. 2018 Jan 25;5(Pt 2):166-171. doi: 10.1107/S2052252517017961. eCollection 2018 Mar 1.PMID: 29765606  

Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse
Li J., Shalev-Benami M., Sando R., Jiang X., Kibrom A., Wang J., Leon K., Katanski C., Nazarko O., Lu Y., Südhof TC., Skiniotis G., Araç D.
Cell. 2018 Apr 19;173(3):735-748.e15. doi: 10.1016/j.cell.2018.03.036. PMID: 29677516
UChicago News
F1000 recommendation

Salzman, GS., Zhang S., Gupta A., Koide A., Koide S., Araç D. Stachel-independent modulation of GPR56/ADGRG1 signaling by synthetic ligands directed to its extracellular region. PNAS. 2017. PMID: 28874577