Picture of Andrew Kruse

Andrew Kruse, Ph.D.

Professor of Biological Chemistry and Molecular Pharmacology

Our research aims to elucidate the molecular basis of membrane protein signaling using techniques including protein engineering, structural biology, and pharmacology.

Research:

Signal transduction across cell membranes plays a central role in human physiology and disease, yet the mechanistic details underlying transmembrane signaling remain poorly understood. Our research aims to elucidate the molecular basis of membrane protein signaling using techniques including protein engineering, structural biology, and pharmacology. In particular, we are focused on the study of proteins important in human health and disease, including G protein-coupled receptors and other proteins that regulate neurotransmission and metabolic homeostasis.

G protein-coupled receptors (GPCRs) are cell-surface receptors that regulate neurotransmission, cardiovascular function, metabolic homeostasis, and many other physiological processes. Due to their central role in human physiology, these receptors are among the most important targets of therapeutic drugs, and are they among the most extensively studied proteins. To better understand GPCR signal transduction at a molecular level, we are using structural biology and biophysical methods to study model GPCRs such as muscarinic acetylcholine receptors. In addition, we are using new approaches in combinatorial biology to facilitate structural studies and to create protein ligands of GPCRs.

We are also interested in signal transduction pathways that remain less extensively studied than GPCRs, particularly receptors involved in the regulation of human metabolic homeostasis. In the long term, we hope to leverage our understanding of molecular signal transduction to guide the development of new and better therapeutics that modulate these pathways.

Address: 

Room SGM - 227

250 Longwood Avenue

Boston, MA 02115

Publications View
Structural Basis of Smoothened Activation in Hedgehog Signaling.
Authors: Authors: Huang P, Zheng S, Wierbowski BM, Kim Y, Nedelcu D, Aravena L, Liu J, Kruse AC, Salic A.
Cell
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In Vivo Evidence for ATPase-Dependent DNA Translocation by the Bacillus subtilis SMC Condensin Complex.
Authors: Authors: Wang X, Hughes AC, Brandão HB, Walker B, Lierz C, Cochran JC, Oakley MG, Kruse AC, Rudner DZ.
Mol Cell
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Loss of specificity variants of WzxC suggest that substrate recognition is coupled with transporter opening in MOP-family flippases.
Authors: Authors: Sham LT, Zheng S, Yakhnina AA, Kruse AC, Bernhardt TG.
Mol Microbiol
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Structural Basis of Smoothened Activation in Hedgehog Signaling.
Authors: Authors: Huang P, Zheng S, Wierbowski BM, Kim Y, Nedelcu D, Aravena L, Liu J, Kruse AC, Salic A.
Cell
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Structure and mutagenic analysis of the lipid II flippase MurJ from Escherichia coli.
Authors: Authors: Zheng S, Sham LT, Rubino FA, Brock KP, Robins WP, Mekalanos JJ, Marks DS, Bernhardt TG, Kruse AC.
Proc Natl Acad Sci U S A
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Investigating isoindoline, tetrahydroisoquinoline, and tetrahydrobenzazepine scaffolds for their sigma receptor binding properties.
Authors: Authors: Linkens K, Schmidt HR, Sahn JJ, Kruse AC, Martin SF.
Eur J Med Chem
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Sortase ligation enables homogeneous GPCR phosphorylation to reveal diversity in ß-arrestin coupling.
Authors: Authors: Staus DP, Wingler LM, Choi M, Pani B, Manglik A, Kruse AC, Lefkowitz RJ.
Proc Natl Acad Sci U S A
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Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis.
Authors: Authors: Sjodt M, Brock K, Dobihal G, Rohs PDA, Green AG, Hopf TA, Meeske AJ, Srisuknimit V, Kahne D, Walker S, Marks DS, Bernhardt TG, Rudner DZ, Kruse AC.
Nature
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Structure-based discovery of selective positive allosteric modulators of antagonists for the M2 muscarinic acetylcholine receptor.
Authors: Authors: Korczynska M, Clark MJ, Valant C, Xu J, Moo EV, Albold S, Weiss DR, Torosyan H, Huang W, Kruse AC, Lyda BR, May LT, Baltos JA, Sexton PM, Kobilka BK, Christopoulos A, Shoichet BK, Sunahara RK.
Proc Natl Acad Sci U S A
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Structural Basis for G Protein-Coupled Receptor Signaling.
Authors: Authors: Erlandson SC, McMahon C, Kruse AC.
Annu Rev Biophys
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