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Cryo-EM structure determination of the laminin polymer node


EMSL Project ID
51312

Abstract

Laminins (Lms) are heterotrimeric glycoproteins required for the assembly of basement membranes (BMs) and are involved in embryonic differentiation, tissue maintenance and wound repair. Defective Lms disrupt BMs to cause diseases of muscle, nerve, brain, kidney, eye and skin. Most Lms, i.e. those with three short arms containing LEa domains each tipped by an LN domain, undergo polymerization to form a sheet-like extracellular matrix that becomes anchored to the cytoskeleton through cell receptors. The Lm isoforms have tunable polymerization characteristics predicted to alter BM stiffness, hence modulate cell signaling. In addition, short homologous LN-LEa proteins such as netrin4 interfere with polymer assembly by competitive inhibition. Our previous work established that the Ln polymer is formed by the joining of alpha, beta and gamma LN domains to form Lm-111 polymer nodes. We propose to determine cryo-EM structures of the Lm111, netrin4-Lm inhibitory complex and defective neuromuscular and kidney laminin polymer nodes.

Project Details

Start Date
2020-03-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Arek Kulczyk
Institution
Rutgers University

Team Members

Janette Myers
Institution
Oregon Health & Science University