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NLM Intramural Research Program

About

Research Interests

No introductory-level biochemistry textbook is complete without a chapter about how a protein’s primary sequence of amino acids determines its fold. Despite much technical progress, however, solving protein structures experimentally remains very laborious and expensive, and knowing the structures of diverse proteins is crucial for both basic research and drug design. Thus, computational prediction of a protein’s structure from its amino acid sequence is a challenge of major importance.

Nearly all computational work so far has focused on predicting a single protein structure from the protein’s amino acid sequence. Dr. Porter’s research challenges the one-sequence-one-structure paradigm. In a recent publication, Loren Looger and she found nearly 100 examples of proteins that can adopt more than one stable fold. This structural heterogeneity allows proteins either to perform more than one function or to be highly regulated in cells. Through the NLM Intramural Research Program, her lab is developing data-driven computational approaches to predict which amino acid sequences can switch folds. She and her lab members validate these predictions experimentally at the National Heart, Lung, and Blood Institute (NHLBI).

This basic research has significant implications for human health. A number of fold-switching proteins are associated with diseases such as cancer, autoimmune disorders, and bacterial and viral infections. Right now, very little is known about how these proteins work. Understanding their mechanisms could lead to development of new therapeutics.

Biography

Dr. Lauren Porter is a Stadtman Tenure-track Investigator with a primary appointment at NLM and a secondary appointment at NHLBI. Prior to coming to the NIH, Dr. Porter spent 7 years studying the biological and biophysical properties of fold-switching proteins, first at the University of Maryland and then at the Howard Hughes Medical Institute, Janelia Research Campus. She is the corresponding author of several recent papers reporting the results of this research. One of them, published in PNAS, was highlighted by two members of Faculty of 1000. For her research on protein fold switching, Dr. Porter has received the Maryland Academy of Science’s Outstanding Young Scientist Award (2015) and a National Research Service Award (2014), and she has presented her research at nearly 20 national and international conferences.

Publications

Mishra S, Looger LL, Porter LL. Inaccurate secondary structure predictions often indicate protein fold switching. Protein Sci. 2019 Aug;28(8):1487-1493. doi: 10.1002/pro.3664. Epub 2019 Jun 17. PubMed PMID: 31148305; PubMed Central PMCID: PMC6635839.

Molineros JE, Looger LL, Kim K, Okada Y, Terao C, Sun C, Zhou XJ, Raj P, Kochi Y, Suzuki A, Akizuki S, Nakabo S, Bang SY, Lee HS, Kang YM, Suh CH, Chung WT, Park YB, Choe JY, Shim SC, Lee SS, Zuo X, Yamamoto K, Li QZ, Shen N, Porter LL, Harley JB, Chua KH, Zhang H, Wakeland EK, Tsao BP, Bae SC, Nath SK. Amino acid signatures of HLA Class-I and II molecules are strongly associated with SLE susceptibility and autoantibody production in Eastern Asians. PLoS Genet. 2019 Apr;15(4):e1008092. doi: 10.1371/journal.pgen.1008092. eCollection 2019 Apr. PubMed PMID: 31022184; PubMed Central PMCID: PMC6504188.

Porter LL, Looger LL. Extant fold-switching proteins are widespread. Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):5968-5973. doi: 10.1073/pnas.1800168115. Epub 2018 May 21. PubMed PMID: 29784778; PubMed Central PMCID: PMC6003340.

Porter LL, He Y, Chen Y, Orban J, Bryan PN. Subdomain interactions foster the design of two protein pairs with ∼80% sequence identity but different folds. Biophys J. 2015 Jan 6;108(1):154-62. doi: 10.1016/j.bpj.2014.10.073. PubMed PMID: 25564862; PubMed Central PMCID: PMC4286614.

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