Source: Interfolio F180
Marco Mravic, PhD
Research Focus
Mravic lab uses protein design and integrative computational approaches to challenge our understanding of biomolecular structure, function, and physical chemistry - mainly within the cellular membrane environment.
The three focus areas of our group are
(1) Designing of small synthetic membrane proteins as simple model systems to test fundamental biophysical questions governing molecular structure and function.
(2) De novo design and high-throughput engineering of custom chemical biology tools targeting membrane proteins directly at their lipid-embedded regions to probe molecular mechanism and therapeutic opportunities.
(3) Molecular modeling and dynamics simulations that integrate diverse experimental data to better understand critical molecular events at cellular membranes
Our lab's mission is to take an engineering approach (with new tool molecules or custom model systems) to investigating important biophysical principles underlying protein structure and activity in lipid as well as molecular determinants of disease. Our protein design efforts aim to engineer and study simplified model systems or novel chemical tools that allow us to proactively hypothesize, test, and establish chemical 'rules' for structure and function within the distinct environment of cellular membranes. These rules emerge through integrating cellular and biophysical experiments with bioinformatics, all-atom simulations, and theoretical energy calculations. The lab's experimental expertise to interrogate membrane protein structure and function are highly multi-disciplinary, ranging from total protein chemical synthesis, structural biology (X-ray, NMR, cryo-EM), cell-based assays, and in vitro biophysics.
Education
B.S. (Chemical Engineering), University of California, Los Angeles, 2014Ph.D. (Molecular Biophysics), University of California, San Francisco, 2020
Awards & Professional Activities
Minority Access to Research Careers (MARC) U*Star Trainee, 2012-14, UCLAHoward Hughes Medical Institute (HHMI) Gilliam Fellow, 2017-20, UCSF
Selected Publications
Mravic, Marco; Thomaston, Jessica L.; Tucker, Maxwell; Solomon, Paige E.; Liu, Lijun; Degrado, William F. Packing of apolar side chains enables accurate design of highly stable membrane proteins.. Science (New York, N.Y.) 2019, 363, 1418-1423.
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Litvinov, Rustem I.; Mravic, Marco; Zhu, Hua; Weisel, John W.; Degrado, William F.; Bennett, Joel S. Unique transmembrane domain interactions differentially modulate integrin avß3 and aIIbß3 function.. Proceedings of the National Academy of Sciences of the United States of America 2019, 116, 12295-12300.
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Dang, Bobo; Mravic, Marco; Hu, Hailin; Schmidt, Nathan W.; Mensa, Bruk; Degrado, William F. SNAC-tag for Sequence-specific Chemical Protein Cleavage.. Nature methods 2019, 16, 319-322.
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Mravic, Marco; Hu, Hailin; Lu, Zhenwei; Bennett, Joel S.; Sanders, Charles R.; Orr, A W.; Degrado, William F. De novo designed transmembrane peptides activating the a5ß1 integrin.. Protein engineering, design & selection : PEDS 2018, 31, 181-190.
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Maillie, Colleen; Golden, Jay; Wilson, Ian A.; Ward, Andrew B.; Mravic, Marco Ab initioprediction of specific phospholipid complexes and membrane association of HIV-1 MPER antibodies by multi-scale simulations. eLife (Reviewed Preprint) 2023.
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Mravic, Marco; Le, H; Kratochvil, H T.; Hu, H; Nick, S E.; Bai, W; Edwards, A; Jo, H; Wu, Y; DiMaio, D; DeGrado, W F. Designed Transmembrane Proteins Inhibit the Erythropoietin Receptor in a Custom Binding Topology. Nature Chemical Biology 2024.