pew-lecture-2016



pew-lecture-2016

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pew-lecture-2016

Lecture given at Pew meeting, 2016

On Github harmsm / pew-lecture-2016

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

The past is the key to the present

adapted from video by MrOwnerandPwner

The past is the key to the present

adapted from video by MrOwnerandPwner

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