David Atkinson, PhD

Professor, Physiology & Biophysics

David Atkinson
(617) 638-4015
700 Albany St Ctr for Adv Biomed Res

Biography

The long standing objectives of my research are to provide the detailed structural and dynamic description of the plasma lipoproteins and apolipoproteins that is crucial to understanding the molecular mechanisms of such physiological processes as lipoprotein formation, receptor interactions, lipoprotein inter-conversions, and apoprotein exchange together with the changes in these characteristics that underlie the pathophysiology of atherosclerosis. Our research has been a component of a Program Project since its inception in 1980 and I have led the Program since 2001, taking over from Dr. Small. Building on initial training in diffraction methods and biophysics, I have maintained and expanded my expertise in state-of-the-art methods of molecular biophysics and structural biology including crystallography, electron microscopy/image processing, calorimetry and thermodynamics, circular dichroism, and molecular modeling/mechanics to probe the structure-function relationships of the lipoproteins and apolipoproteins. This includes a one year sabbatical at the MRC Laboratory of Molecular Biology, Cambridge, England developing electron microscopy.

My long standing research program has involved many collaborations with current and past Program Project investigators, particularly Drs. Gursky, Small, and McKnight. Our previous work over more than three decades has focused on the structural and thermodynamic properties of specific lipoproteins (HDL and LDL), and apolipoproteins, particularly apoA-1, together with studies of the LDL receptor. We derived the first structural description of HDL, nascent HDL and LDL using x-ray methods. Our mutation studies of the conformation, stability, and lipid binding properties have contributed to providing a framework for understanding the molecular properties of apoA-1. Furthermore, our studies of peptides representing segments of apoA-1, together with “idealized” sequence models, have provided information on the role of specific residues and domains, and their interactions in the structure and stability of apoA-1. For LDL, we pioneered the use of cryo-electron microscopy to study LDL structure and used mAb labeling to investigate the topology of apoB. In collaborations with Dr. Graham Shipley, a long standing collaborator and colleague, our approach for the LDL receptor has focused on structural studies of the functional extracellular domain of the receptor reconstituted into lipid vesicles.

Other Positions

  • Chair, Physiology & Biophysics, Boston University School of Medicine
  • Research Professor, Biochemistry, Boston University School of Medicine
  • Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences

Education

  • Council for National Academic Awards, PhD
  • The City University, BSc

Publications

  • Published on 2/13/2017

    Gorshkova IN, Atkinson D. Increased Binding of Apolipoproteins A-I and E4 to Triglyceride-Rich Lipoproteins is linked to Induction of Hypertriglyceridemia. JSM Atheroscler. 2017; 2(2). PMID: 28597004.

    Read at: PubMed
  • Published on 6/17/2016

    Mei X, Liu M, Herscovitz H, Atkinson D. Probing the C-terminal domain of lipid-free apoA-I demonstrates the vital role of the H10B sequence repeat in HDL formation. J Lipid Res. 2016 Aug; 57(8):1507-17. PMID: 27317763.

    Read at: PubMed
  • Published on 6/3/2015

    Mei X, Atkinson D. Lipid-free Apolipoprotein A-I Structure: Insights into HDL Formation and Atherosclerosis Development. Arch Med Res. 2015 Jul; 46(5):351-60. PMID: 26048453.

    Read at: PubMed
  • Published on 6/11/2014

    Gorshkova IN, Mei X, Atkinson D. Binding of human apoA-I[K107del] variant to TG-rich particles: implications for mechanisms underlying hypertriglyceridemia. J Lipid Res. 2014 Sep; 55(9):1876-85. PMID: 24919401.

    Read at: PubMed
  • Published on 4/28/2014

    Das M, Mei X, Jayaraman S, Atkinson D, Gursky O. Amyloidogenic mutations in human apolipoprotein A-I are not necessarily destabilizing - a common mechanism of apolipoprotein A-I misfolding in familial amyloidosis and atherosclerosis. FEBS J. 2014 Jun; 281(11):2525-42. PMID: 24702826.

    Read at: PubMed
  • Published on 12/5/2013

    Wang L, Mei X, Atkinson D, Small DM. Surface behavior of apolipoprotein A-I and its deletion mutants at model lipoprotein interfaces. J Lipid Res. 2014 Mar; 55(3):478-92. PMID: 24308948.

    Read at: PubMed
  • Published on 9/13/2013

    Gursky O, Jones MK, Mei X, Segrest JP, Atkinson D. Structural basis for distinct functions of the naturally occurring Cys mutants of human apolipoprotein A-I. J Lipid Res. 2013 Dec; 54(12):3244-57. PMID: 24038317.

    Read at: PubMed
  • Published on 12/28/2012

    Khachfe HM, Atkinson D. Conformation and stability properties of B17: II. Analytical investigations using differential scanning calorimetry. Eur Biophys J. 2013 Apr; 42(4):309-14. PMID: 23271513.

    Read at: PubMed
  • Published on 7/25/2012

    Khachfe HM, Atkinson D. Conformation and stability properties of B17: I. Analytical investigations using circular dichroism. Eur Biophys J. 2012 Aug; 41(8):639-46. PMID: 22828936.

    Read at: PubMed
  • Published on 12/29/2011

    Gursky O, Mei X, Atkinson D. The crystal structure of the C-terminal truncated apolipoprotein A-I sheds new light on amyloid formation by the N-terminal fragment. Biochemistry. 2012 Jan 10; 51(1):10-8. PMID: 22229410.

    Read at: PubMed

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