Evolution of multifunctionality in S100 proteins
Mike Harms
University of Oregon
Pew Meeting, 2016
Projects in the Harms lab
Luke Wheeler: Specificity from promiscuous ancestral proteins
Zach Sailer: High-dimensional genotype phenotype maps
Andrea Loes: How did multifunctionality in evolve for calprotectin?
Calprotectin is a multifunctional protein
Calprotectin is a multifunctional protein
Calprotectin is a multifunctional protein
Calprotectin is a multifunctional protein
Calprotectin is a multifunctional protein
How are these diverse functions achieved by 207 amino acids?
How did this evolve?
4GGF, Damo ... Chazin (2013) PNAS 110(10:3841-3846
Trace the evolution of each function
Trace the evolution of each function
Trace the evolution of each function
Trace the evolution of each function
Trace the evolution of each function
Evolution as acquisition of new protein partners?
CP has a C-terminal tail that becomes ordered with $Zn^{2+}$ binding.
Tail is not necessary for TLR4 activation
Tail is not necessary for TLR4 activation
Tail is not necessary for TLR4 activation
Calprotectin is well-behaved and soluble...
Until you add $Ca^{2+}$ and $Zn^{2+}$
Amyloid calprotectin effectively activates TLR4
Evolution of multifunctionality through an amyloid?
People
Luke Wheeler
Andrea Loes
Zach Sailer
Joseph Harman
Jamie Bridgham
Prof. Jim Prell
Undergraduates: Bram Ricketts, Ran Shi, Hiranmayi Duvvuri, Sarina Pollat, Abigal Tamil, Jaclyn Smith
Funding
We use ancestral sequence reconstruction to trace the evolution of proteins
We use ancestral sequence reconstruction to trace the evolution of proteins
We use ancestral sequence reconstruction to trace the evolution of proteins
We use ancestral sequence reconstruction to trace the evolution of proteins
We use ancestral sequence reconstruction to trace the evolution of proteins
We use ancestral sequence reconstruction to trace the evolution of proteins
We use ancestral sequence reconstruction to trace the evolution of proteins