TCB Publications - Abstract

Venkat Maruthamuthu, Klaus Schulten, and Deborah Leckband. Elasticity and rupture of a multi-domain neural cell adhesion molecule complex. Biophysical Journal, 96:3005-3014, 2009. (PMC: 2718298)

MARU2009 The neural cell adhesion molecule (NCAM) plays an important role in nervous system development. In one binding configuration, it forms complexes between its terminal domains Ig1 and Ig2. When NCAM of cell A and cell B connect to each other through complexes Ig12(A)/Ig12(B), the relative mobility of cells A and B and membrane tension exerts mechanical strain on the Ig12(A)/Ig12(B) complex. Here we investigate the response of the complex to such strain, using steered molecular dynamics. Starting from a recent crystallographic structure of the complex from the Ig1-Ig2-Ig3 fragment, we first demonstrate that the complex, which differs in dimensions from a previous structure from the Ig1-Ig2 fragment in the crystal environment, actually assumes the same extension when equilibrated in solvent. We then show that, upon pulling the Ig12(A)/Ig12(B) complexes apart with forces 50-70pN, they exhibit linear elasticity involving extension due to reordering of domains Ig1(A) and Ig2(A) (same for B). When higher forces are applied, the complex ruptures, i.e., Ig12(A) and Ig12(B) separate. The interfacial interactions between Ig12(A) and Ig12(B) are monitored throughout elastic extension and rupture. E16, F19, K98, and L175 are identified as key side groups and their bonding properties are described in detail.

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