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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.

Consortia Investigators

  • University of Kansas Medical Center
    Alan S. L. Yu
  • University of Pittsburgh
    Rob D. Coalson

Contact Information

Alan S. L. Yu

Research Description

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.


Key Publications
  1. Yu ASL, Cheng, MH, Angelow S, Günzel D, Kanzawa SA, Schneeberger EE, Fromm M, Coalson RD.
    Molecular basis for cation selectivity in claudin-2-based paracellular pores: Identification of an electrostatic interaction site.

    J Gen Physiol,133: 111-127, 2009. (PubMed ID: 19114638).
  2. Angelow S, Yu ASL.
    Structure-function studies of claudin extracellular domains by cysteine-scanning mutagenesis.

    J Biol Chem,284(42):29205-17, 2009. (PubMed ID: 19690347).
  3. Yu ASL, Cheng MH, Coalson RD.
    Calcium inhibits paracellular sodium conductance through claudin-2 by competitive binding.

    J Biol Chem, in press. (PubMed ID: 20807759).

Structures, Targets, Publications and Technologies

TJMP Targets in TargetTrack

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Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health