Professional Bio
Contribution to Science. In the early 1970s the structures of membrane proteins and plasma lipoproteins were unknown. I played a major role in resolving that conundrum when I published four seminal papers demonstrating, for the first time, the basic structural principles underlying the supramolecular assembly of proteins and lipids in membranes-the transmembrane hydrophobic alpha-helix [1-2]-and in lipoproteins-the surface-associating amphipathic alpha-helix [3-4]. I then focused on the role of the amphipathic alpha-helix in plasma lipoproteins. I took the high-risk approach of using a computational approach-molecular dynamics simulations-in combination with more traditional wet lab methods, to explore the dynamic all atom structure of both discoidal and spheroidal (circulating) HDL [5-6]. Using similar analytical approaches, I published what has proven to be the most influential analysis of the apolipoprotein B protein structure of LDL so far [7,8]. At present, I am focused on understanding the biomolecular assembly of HDL by the transmembrane ABCA1 [9]. My H-index is 69. Grant success. Since 1974 I have been the PI on a total of ten separate R01 grants, a NHLBI shared facility grant and two program projects; the initial was funded to its 25th year. Key publications 1. Segrest JP, Kahane I, Jackson RL, Marchesi VT. Major glycoprotein of the human erythrocyte membrane: evidence for an amphipathic molecular structure. Arch Biochem Biophys 1973; 155(1): 167- 183. PMID: 4712445 (253 citations) 2. Segrest JP, Gulik-Krzywicki T, Sardet C. Association of the membrane-penetrating polypeptide segment of the human erythrocyte MN-glycoprotein with phospholipid bilayers. I. Formation of freeze-etch intramembranous particles. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3294-8. PubMed PMID: 4528433; PubMed Central PMCID: PMC388672. (134 citations) 3. Segrest JP, Jackson RL, Morrisett JD, Gotto AM Jr. A molecular theory of lipid-protein interactions in the plasma lipoproteins. FEBS Lett. 1974 Jan 15;38(3):247-58. PubMed PMID: 4368333. (659 citations) 4. Segrest JP, Feldmann RJ. Membrane proteins: amino acid sequence and membrane penetration. J Mol Biol. 1974 Aug 25;87(4):853-8. PubMed PMID: 4427380. (167 citations) 5. Segrest JP, Jones MK, Klon AE, Sheldahl CJ, Hellinger M, De Loof H, Harvey SC. A detailed molecular belt model for apolipoprotein A-I in discoidal high density lipoprotein. J Biol Chem. 1999 Nov 5;274(45):31755-8. PubMed PMID: 10542194. (298 citations) 6. Gu F, Jones MK, Chen J, Patterson JC, Catte A, Jerome WG, Li L, Segrest JP. Structures of discoidal high density lipoproteins: a combined computational-experimental approach. J Biol Chem. 2010 Feb 12;285(7):4652-65. PubMed PMID: 19948731; PubMed Central PMCID: PMC2836071. (66 citations) 7. Segrest, J. P., Tang, C., Song, H. D., Jones, M. K., Davidson, W. S., Aller, S. G., and Heinecke, J. W. (2022) ABCA1 is an extracellular phospholipid translocase. Nature communications 13, 48. 8. Segrest JP, Jones MK, Mishra VK, Anantharamaiah GM, Garber DW. apoB-100 has a pentapartite structure composed of three amphipathic alpha-helical domains alternating with two amphipathic beta- strand domains. Detection by the computer program LOCATE. Arterioscler Thromb. 1994 Oct;14(10):1674-85. PubMed PMID: 7918318. (163 citations) 9. Segrest JP, Jones MK, De Loof, H, Dashti N. Structure of apolipoprotein B-100 in low density lipoproteins. J Lipid Res 2001; 42(9): 1346-1367. PMID: 11518754 (375 citations)
Publications
Education
MD - Vanderbilt University, 1967
Fellowship - Biochemistry - Vanderbilt University, 1967
Fellowship - Postdoc Biochemistry - Vanderbilt University, 1968
PhD - Biochemistry - Vanderbilt University, 1969
Residency - Pathology - Vanderbilt University, 1970
Contact
Email
Kimryn.Rathmell@Vumc.Org
Address
777 Preston Research Building
2220 Pierce Ave
Nashville, TN 37232-6307