id="title" class="nomar"Structure-Function Studies of Tight Junction Membrane Proteins
This biological project consists of investigators from the University of Kansas Medical Center and the University of Pittsburgh. It is partnered with the PSI Membrane Protein Structure Determination Center CSMP.
- University of Kansas Medical Center
Alan S. L. Yu
- University of Pittsburgh
Rob D. Coalson
Alan S. L. Yu
Tight junctions have three critically important functions in both epithelia and endothelia. Tight junctions form the paracellular barrier that separates body compartments, they act as a fence that maintains apical-basolateral polarity of the cell, and they have paracellular pores that allow selective permeation of ions and small molecules across the cell monolayer. Three integral membrane proteins are thought to play a central role in these functions of the tight junction and hence are of high biological interest: claudin (a multigene family with 24 members), occludin, and tricellulin. Our long-term goal is to solve the structure of each of these proteins at high resolution and to use structure-guided mutagenesis to elucidate the structural mechanisms underlying their unique functions. To this end, we have partnered with Dr. Robert Stroud and the Center for Structures of Membrane Proteins (CSMP) to express, purify and crystallize these proteins. Our team's expertise in assaying paracellular pore function includes electrophysiological methods, freeze-fracture electron microscopy, and hybrid molecular/Brownian dynamics modeling of pore function.
Structures, Targets, Publications and Technologies
(to be provided)