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Grabe

Michael Grabe, PhD

Professor
Cardiovascular Research Institute
Address: 
555 Mission Bay Blvd South, Rm 452T
UCSF Box 3122
San Francisco, CA 94158
United States
Phone: 
+1 415 502-2874

Research Summary:
Our lab uses computational methods to understand biological phenomena. We are primarily interested in the mechanical operation of ion channels and transporters, which move ions and small molecules across membranes. Additionally, we use theoretical approaches to explore how these membrane proteins work together to regulate ion homeostasis in organelles such as the lysosome and Golgi. Lastly, we are developing methodologies for predicting the stability of membrane proteins to understand how mutations give rise to a loss of function, improper trafficking or degradation.

Education and Training: 
07/2021
University of California, San Francisco
Diversity, Equity, and Inclusion Champion Training
07/2021
University of California, San Francisco
Diversity, Equity, and Inclusion Champion Training
Research Activities And Funding: 
Jan 1, 2021 - Nov 30, 2024

Ion permeation, lipid flipping, and membrane remodeling by TMEM16 proteins

NIH R01GM137109

Role: Principal Investigator
Sep 1, 2012 - Jul 31, 2015

Computer simulations of lysosomal and osteoclast microphysiology

NIH R21GM100224

Role: Principal Investigator
Publications: 

Robust lipid scrambling by TMEM16 proteins requires an open groove and thin membrane.

bioRxiv : the preprint server for biology

Stephens CA, van Hilten N, Zheng L, Grabe M

Membrane curvature sensing and symmetry breaking of the M2 proton channel from Influenza A.

eLife

Lincoff J, Helsell CVM, Marcoline FV, Natale AM, Grabe M

Remodelling of the translatome controls diet and its impact on tumorigenesis.

Nature

Yang H, Zingaro VA, Lincoff J, Tom H, Oikawa S, Oses-Prieto JA, Edmondson Q, Seiple I, Shah H, Kajimura S, Burlingame AL, Grabe M, Ruggero D

Structure of the human K2P13.1(THIK-1) channel reveals a novel hydrophilic pore restriction and lipid cofactor site.

bioRxiv : the preprint server for biology

Roy-Chowdhury S, Jang S, Abderemane-Ali F, Naughton F, Grabe M, Minor DL

Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT.

Nature communications

Khan F, Elgeti M, Grandfield S, Paz A, Naughton FB, Marcoline FV, Althoff T, Ermolova N, Wright EM, Hubbell WL, Grabe M, Abramson J

Brominated lipid probes expose structural asymmetries in constricted membranes.

Nature structural & molecular biology

Moss FR, Lincoff J, Tucker M, Mohammed A, Grabe M, Frost A

Regulation of the mammalian-brain V-ATPase through ultraslow mode-switching.

Nature

Kosmidis E, Shuttle CG, Preobraschenski J, Ganzella M, Johnson PJ, Veshaguri S, Holmkvist J, Møller MP, Marantos O, Marcoline F, Grabe M, Pedersen JL, Jahn R, Stamou D

Quaternary structure independent folding of voltage-gated ion channel pore domain subunits.

Nature structural & molecular biology

Arrigoni C, Lolicato M, Shaya D, Rohaim A, Findeisen F, Fong LK, Colleran CM, Dominik P, Kim SS, Schuermann JP, DeGrado WF, Grabe M, Kossiakoff AA, Minor DL

Mitochondrial uncouplers induce proton leak by activating AAC and UCP1.

Nature

Bertholet AM, Natale AM, Bisignano P, Suzuki J, Fedorenko A, Hamilton J, Brustovetsky T, Kazak L, Garrity R, Chouchani ET, Brustovetsky N, Grabe M, Kirichok Y

Berkeley Madonna Version 10-A simulation package for solving mathematical models.

CPT: pharmacometrics & systems pharmacology

Marcoline FV, Furth J, Nayak S, Grabe M, Macey RI

Taking the Monte-Carlo gamble: How not to buckle under the pressure!

Journal of computational chemistry

Gomez YK, Natale AM, Lincoff J, Wolgemuth CW, Rosenberg JM, Grabe M

Elucidation of the molecular interactions that enable stable assembly and structural diversity in multicomponent immune receptors.

Proceedings of the National Academy of Sciences of the United States of America

Fong LK, Chalkley MJ, Tan SK, Grabe M, DeGrado WF

Inroads into Membrane Physiology through Transport Nanomachines.

Journal of molecular biology

Stockbridge RB, Gaudet R, Grabe M, Minor DL

Genetically Encoded, pH-Sensitive mTFP1 Biosensor for Probing Lysosomal pH.

ACS sensors

Chin MY, Patwardhan AR, Ang KH, Wang AL, Alquezar C, Welch M, Nguyen PT, Grabe M, Molofsky AV, Arkin MR, Kao AW

Allosteric cooperation in a de novo-designed two-domain protein.

Proceedings of the National Academy of Sciences of the United States of America

Pirro F, Schmidt N, Lincoff J, Widel ZX, Polizzi NF, Liu L, Therien MJ, Grabe M, Chino M, Lombardi A, DeGrado WF

K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions.

Science advances

Lolicato M, Natale AM, Abderemane-Ali F, Crottès D, Capponi S, Duman R, Wagner A, Rosenberg JM, Grabe M, Minor DL

A kinetic mechanism for enhanced selectivity of membrane transport.

PLoS computational biology

Bisignano P, Lee MA, George A, Zuckerman DM, Grabe M, Rosenberg JM

A systems-biology approach to molecular machines: Exploration of alternative transporter mechanisms.

PLoS computational biology

George A, Bisignano P, Rosenberg JM, Grabe M, Zuckerman DM

EmrE reminds us to expect the unexpected in membrane transport.

The Journal of general physiology

Grabe M, Zuckerman DM, Rosenberg JM

Protons in small spaces: Discrete simulations of vesicle acidification.

PLoS computational biology

Singh A, Marcoline FV, Veshaguri S, Kao AW, Bruchez M, Mindell JA, Stamou D, Grabe M

Biophysics at the coffee shop: lessons learned working with George Oster.

Molecular biology of the cell

Igoshin OA, Chen J, Xing J, Liu J, Elston TC, Grabe M, Kim KS, Nirody JA, Rangamani P, Sun SX, Wang H, Wolgemuth C

Harmonizing Experimental Data with Modeling to Predict Membrane Protein Insertion in Yeast.

Biophysical Journal

Guerriero CJ, Gomez YK, Daskivich GJ, Reutter KR, Augustine AA, Weiberth KF, Nakatsukasa K, Grabe M, Brodsky JL

A multiscale model of mechanotransduction by the ankyrin chains of the NOMPC channel.

The Journal of general physiology

Argudo D, Capponi S, Bethel NP, Grabe M

Chemically induced vesiculation as a platform for studying TMEM16F activity.

Proceedings of the National Academy of Sciences of the United States of America

Han TW, Ye W, Bethel NP, Zubia M, Kim A, Li KH, Burlingame AL, Grabe M, Jan YN, Jan LY

Inhibitor binding mode and allosteric regulation of Na+-glucose symporters.

Nature communications

Bisignano P, Ghezzi C, Jo H, Polizzi NF, Althoff T, Kalyanaraman C, Friemann R, Jacobson MP, Wright EM, Grabe M

Cilia-Associated Oxysterols Activate Smoothened.

Molecular cell

Raleigh DR, Sever N, Choksi PK, Sigg MA, Hines KM, Thompson BM, Elnatan D, Jaishankar P, Bisignano P, Garcia-Gonzalo FR, Krup AL, Eberl M, Byrne EFX, Siebold C, Wong SY, Renslo AR, Grabe M, McDonald JG, Xu L, Beachy PA, Reiter JF

Entry from the Lipid Bilayer: A Possible Pathway for Inhibition of a Peptide G Protein-Coupled Receptor by a Lipophilic Small Molecule.

Biochemistry

Bokoch MP, Jo H, Valcourt JR, Srinivasan Y, Pan AC, Capponi S, Grabe M, Dror RO, Shaw DE, DeGrado WF, Coughlin SR

Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site.

Nature communications

Wahlgren WY, Dunevall E, North RA, Paz A, Scalise M, Bisignano P, Bengtsson-Palme J, Goyal P, Claesson E, Caing-Carlsson R, Andersson R, Beis K, Nilsson UJ, Farewell A, Pochini L, Indiveri C, Grabe M, Dobson RCJ, Abramson J, Ramaswamy S, Friemann R

Conformational transitions of the sodium-dependent sugar transporter, vSGLT.

Proceedings of the National Academy of Sciences of the United States of America

Paz A, Claxton DP, Kumar JP, Kazmier K, Bisignano P, Sharma S, Nolte SA, Liwag TM, Nayak V, Wright EM, Grabe M, Mchaourab HS, Abramson J

The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel.

Neuron

Peters CJ, Gilchrist JM, Tien J, Bethel NP, Qi L, Chen T, Wang L, Jan YN, Grabe M, Jan LY

Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1.

Proceedings of the National Academy of Sciences of the United States of America

Bergdoll LA, Lerch MT, Patrick JW, Belardo K, Altenbach C, Bisignano P, Laganowsky A, Grabe M, Hubbell WL, Abramson J

Transmembrane helix hydrophobicity is an energetic barrier during the retrotranslocation of integral membrane ERAD substrates.

Molecular biology of the cell

Guerriero CJ, Reutter KR, Augustine AA, Preston GM, Weiberth KF, Mackie TD, Cleveland-Rubeor HC, Bethel NP, Callenberg KM, Nakatsukasa K, Grabe M, Brodsky JL

New Continuum Approaches for Determining Protein-Induced Membrane Deformations.

Biophysical Journal

Argudo D, Bethel NP, Marcoline FV, Wolgemuth CW, Grabe M

Atomistic insight into lipid translocation by a TMEM16 scramblase.

Proceedings of the National Academy of Sciences of the United States of America

Bethel NP, Grabe M

A mathematical model of osteoclast acidification during bone resorption.

Bone

Marcoline FV, Ishida Y, Mindell JA, Nayak S, Grabe M

Stochastic steps in secondary active sugar transport.

Proceedings of the National Academy of Sciences of the United States of America

Adelman JL, Ghezzi C, Bisignano P, Loo DD, Choe S, Abramson J, Rosenberg JM, Wright EM, Grabe M

Direct observation of proton pumping by a eukaryotic P-type ATPase.

Science (New York, N.Y.)

Veshaguri S, Christensen SM, Kemmer GC, Ghale G, Møller MP, Lohr C, Christensen AL, Justesen BH, Jørgensen IL, Schiller J, Hatzakis NS, Grabe M, Pomorski TG, Stamou D

Continuum descriptions of membranes and their interaction with proteins: Towards chemically accurate models.

Biochimica et biophysica acta

Argudo D, Bethel NP, Marcoline FV, Grabe M

Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.

Structure (London, England : 1993)

Marcoline FV, Bethel N, Guerriero CJ, Brodsky JL, Grabe M

WESTPA: an interoperable, highly scalable software package for weighted ensemble simulation and analysis.

Journal of chemical theory and computation

Zwier MC, Adelman JL, Kaus JW, Pratt AJ, Wong KF, Rego NB, Suárez E, Lettieri S, Wang DW, Grabe M, Zuckerman DM, Chong LT

De novo design of a transmembrane Zn²⁺-transporting four-helix bundle.

Science (New York, N.Y.)

Joh NH, Wang T, Bhate MP, Acharya R, Wu Y, Grabe M, Hong M, Grigoryan G, DeGrado WF

Structure-guided simulations illuminate the mechanism of ATP transport through VDAC1.

Nature structural & molecular biology

Choudhary OP, Paz A, Adelman JL, Colletier JP, Abramson J, Grabe M

Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia.

Nature medicine

Hong T, Yang H, Zhang SS, Cho HC, Kalashnikova M, Sun B, Zhang H, Bhargava A, Grabe M, Olgin J, Gorelik J, Marbán E, Jan LY, Shaw RM

Continuum approaches to understanding ion and peptide interactions with the membrane.

The Journal of membrane biology

Latorraca NR, Callenberg KM, Boyle JP, Grabe M

Structural determinants of water permeation through the sodium-galactose transporter vSGLT.

Biophysical Journal

Adelman JL, Sheng Y, Choe S, Abramson J, Wright EM, Rosenberg JM, Grabe M

Antibacterial membrane attack by a pore-forming intestinal C-type lectin.

Nature

Mukherjee S, Zheng H, Derebe MG, Callenberg KM, Partch CL, Rollins D, Propheter DC, Rizo J, Grabe M, Jiang QX, Hooper LV

A model of lysosomal pH regulation.

The Journal of general physiology

Ishida Y, Nayak S, Mindell JA, Grabe M

Simulating rare events using a weighted ensemble-based string method.

The Journal of chemical physics

Adelman JL, Grabe M

Membrane bending is critical for the stability of voltage sensor segments in the membrane.

The Journal of general physiology

Callenberg KM, Latorraca NR, Grabe M

Simulations of the alternating access mechanism of the sodium symporter Mhp1.

Biophysical Journal

Adelman JL, Dale AL, Zwier MC, Bhatt D, Chong LT, Zuckerman DM, Grabe M

Raw sewage harbors diverse viral populations.

mBio

Cantalupo PG, Calgua B, Zhao G, Hundesa A, Wier AD, Katz JP, Grabe M, Hendrix RW, Girones R, Wang D, Pipas JM

The mechanism of sodium and substrate release from the binding pocket of vSGLT.

Nature

Watanabe A, Choe S, Chaptal V, Rosenberg JM, Wright EM, Grabe M, Abramson J

Constraint-based, homology model of the extracellular domain of the epithelial Na+ channel α subunit reveals a mechanism of channel activation by proteases.

The Journal of biological chemistry

Kashlan OB, Adelman JL, Okumura S, Blobner BM, Zuzek Z, Hughey RP, Kleyman TR, Grabe M

Water permeation through the sodium-dependent galactose cotransporter vSGLT.

Biophysical Journal

Choe S, Rosenberg JM, Abramson J, Wright EM, Grabe M

APBSmem: a graphical interface for electrostatic calculations at the membrane.

PloS one

Callenberg KM, Choudhary OP, de Forest GL, Gohara DW, Baker NA, Grabe M

Characterization of the PCMBS-dependent modification of KCa3.1 channel gating.

The Journal of general physiology

Bailey MA, Grabe M, Devor DC

Allosteric inhibition of the epithelial Na+ channel through peptide binding at peripheral finger and thumb domains.

The Journal of biological chemistry

Kashlan OB, Boyd CR, Argyropoulos C, Okumura S, Hughey RP, Grabe M, Kleyman TR

The electrostatics of VDAC: implications for selectivity and gating.

Journal of molecular biology

Choudhary OP, Ujwal R, Kowallis W, Coalson R, Abramson J, Grabe M

Getting in sync with dimeric Eg5. Initiation and regulation of the processive run.

The Journal of biological chemistry

Krzysiak TC, Grabe M, Gilbert SP

Electrostatic interactions in the channel cavity as an important determinant of potassium channel selectivity.

Proceedings of the National Academy of Sciences of the United States of America

Bichet D, Grabe M, Jan YN, Jan LY

K+ channel selectivity depends on kinetic as well as thermodynamic factors.

Proceedings of the National Academy of Sciences of the United States of America

Grabe M, Bichet D, Qian X, Jan YN, Jan LY

Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis.

Annals of internal medicine

Nayak S, Olkin I, Liu H, Grabe M, Gould MK, Allen IE, Owens DK, Bravata DM

A quantitative assessment of models for voltage-dependent gating of ion channels.

Proceedings of the National Academy of Sciences of the United States of America

Grabe M, Lecar H, Jan YN, Jan LY

Electrostatic model of S4 motion in voltage-gated ion channels.

Biophysical Journal

Lecar H, Larsson HP, Grabe M

Answers and questions from the KvAP structures.

Neuron

Cohen BE, Grabe M, Jan LY

Protein interactions and membrane geometry.

Biophysical Journal

Grabe M, Neu J, Oster G, Nollert P

Biosynthesis and secretion of pituitary hormones: dynamics and regulation.

Archives of physiology and biochemistry

Moore HP, Andresen JM, Eaton BA, Grabe M, Haugwitz M, Wu MM, Machen TE

Proton leak and CFTR in regulation of Golgi pH in respiratory epithelial cells.

American journal of physiology. Cell physiology

Chandy G, Grabe M, Moore HP, Machen TE

Cystic fibrosis transmembrane conductance regulator and H+ permeability in regulation of Golgi pH.

JOP : Journal of the pancreas

Machen TE, Chandy G, Wu M, Grabe M, Moore HP

Mechanisms of pH regulation in the regulated secretory pathway.

The Journal of biological chemistry

Wu MM, Grabe M, Adams S, Tsien RY, Moore HP, Machen TE

Regulation of organelle acidity.

The Journal of general physiology

Grabe M, Oster G

The mechanochemistry of V-ATPase proton pumps.

Biophysical Journal

Grabe M, Wang H, Oster G

How Fo-ATPase generates rotary torque.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

Oster G, Wang H, Grabe M

Energy transduction in the sodium F-ATPase of Propionigenium modestum.

Proceedings of the National Academy of Sciences of the United States of America

Dimroth P, Wang H, Grabe M, Oster G

Pathways, pathway tubes, pathway docking, and propagators in electron transfer proteins.

Journal of bioenergetics and biomembranes

Curry WB, Grabe MD, Kurnikov IV, Skourtis SS, Beratan DN, Regan JJ, Aquino AJ, Beroza P, Onuchic JN

ORCID: 
0000-0003-3509-5997 Additional info
Faculty Type: 
Core CVRI Faculty