Carl Frieden, Ph.D.

Biochemistry and Molecular Biophysics

Biochemistry, Biophysics, and Structural Biology Program
Molecular Cell Biology Program

  • 314-362-3344

  • 314-362-3342

  • 314-362-7183

  • 8231

  • 215 McDonnell Medical Sciences Building



  • apoE lipoproteins,, intrinsically disordered proteins, amyloid-beta, Alzheimer’s Disease, bacterial infection, curli proteins

  • Protein structure/function relationships

Research Abstract:

There are two major projects in my lab, both of which relate to human disease studied from a biophysical perspective. The first of these is the study of the apolipoprotein E (apoE) family of proteins and their relation to late-onset Alzheimer’s Disease (AD). Of the three isoforms of this 34 kDa protein, which differ only by single amino acid changes, apoE4 is the major risk factor for AD while apoE3, the most common form, is not implicated in developing AD. The majority of those with AD can be correlated with the presence of at least one copy of apoE4. The apoE proteins also bind amyloid-beta (Abeta) found in brain amyloid plaques. We study the differences between the apoE isoforms using biophysical techniques with the goal of understanding why the different apoE isoforms have different functional properties.

The second project involves the study of bacterial proteins involved in biofilm-related infections. Specifically we are interested in adhesive amyloid fibers called curli. Curli fibril formation involves 5 different proteins, two of which, CsgE and CsgF, could be chaperones that bind to and transport of those proteins that are make up the amyloid fiber. We recently determined the structure of CsgE. The two proteins in the fiber, CsgA and CsgB, are intrinsically disordered but form beta strand structures on aggregation. We study the aggregation mechanism of these proteins and their interaction with the chaperonin proteins, CsgE and CsgF. The fifth protein, CsgG, is a pore protein allowing CsgA and CsgB to be exported to the bacterial surface.

Selected Publications:

Q. Shu, A. M. Krezel, Z. Cusumano, J. S. Pinkner, R. Klein, S. J. Hultgren and C. Frieden, (2016) Solution NMR structure of CsgE: Structural insights into a chaperone and regulator protein important for functional amyloid formation Proc Natl Acad Sci USA. 113 7130-7135 PMCID4932985

T. Mondal, H .Wang, G. T. DeKoster, B. Baban, M. L. Gross and C. Frieden. (2016) ApoE: In vitro studies of a small molecule effector. Biochemistry 55 2613-2621 PMCID4976638

C. Frieden. (2015) ApoE: The role of conserved residues in defining function. Prot Sci 24 138-144.PMC4282419

Garai, K and Frieden, C. (2013) Quantitative analysis of the time course of Abeta oligomerization and subsequent growth steps using tetramethylrhodamine-labeled Abeta. Proc Natl Acad Sci 110 3321-3326.PMC3587211

Frieden, C. and Garai.K. (2012) Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer`s disease. Proc Natl Acad Sci (USA) 109 8913-8918.PMC3384159

Huang R, Garai K, Frieden C and Gross M. (2011 Interface determination and dynamics of apolipoprotein E oligomerization by hydrogen deuterium exchange and electron-transfer dissociation mass spectrometry. Biochemistry 50: 9273-9282.

Garai K, Baban B and Frieden C. (2011) Dissociation of apoE oligomers to monomer is required for high affinity binding to phospholipid vesicles. Biochemistry 50: 2550-2558. PMCID: PMC3088999

Baldwin RL, Frieden C and Rose G. (2010) Dry Molten Globule Intermediates and the Mechanism of Protein Unfolding. Proteins: Structure and Function 78 1-13. PMCID: PMC2927783

Garai K, Mustafi SM, Baban B and Frieden C. (2010) Structural differences between apolipoprotein E3 and E4 as measured by 19F- NMR. Protein Sci 19: 66-74. PMCID: PMC2817840

Hu X, Crick SL, Bu G, Frieden C, Pappu RV and Lee J-M. (2009) Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide Proc Natl Acad Sci (USA) 106: 20324-20329. PMCID: PMC2787156

Last Updated: 8/29/2016 9:41:45 AM

Back To Top

Follow us: