Characterization of the neuron-specific L1-CAM cytoplasmic tail: Naturally disordered in solution it exercises different binding modes for different adaptor proteins

Sergiy Tyukhtenko, Lalit Deshmukh, Vineet Kumar, Jeffrey Lary, James Cole, Vance Lemmon, Olga Vinogradova

Research output: Contribution to journalArticle

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Abstract

L1, a highly conserved transmembrane glycoprotein member of the immunoglobulin superfamily of cell adhesion molecules, mediates many developmental processes in the nervous system. Here we present the biophysical characterization and the binding properties of the least structurally defined part of this receptor: its cytoplasmic tail (CT). We have shown by analytical ultracentrifugation and dynamic light scattering experiments that it is mostly monomeric and unstructured in aqueous solution. We have defined by nuclear magnetic resonance the molecular details of L1-CT binding to two major targets: a membrane-cytoskeletal linker (MCL), ezrin, and an endocytosis mediator, AP2. Surprisingly, in addition to the two previously identified ezrin binding motifs, the juxtamembrane and the 1176YRSLE regions, we have discovered a third one, a part of which has been previously associated with binding to another MCL, ankyrin. For the L1 interaction with AP2 we have determined the precise interaction region surrounding the 1176YRSLE binding site and that this overlaps with the second ezrin binding site. In addition, we have shown that the juxtamembrane region of L1-CT has some binding affinity to AP2-μ2, although the specificity of this interaction needs further investigation. These data indicate that L1-CT belongs to the class of intrinsically disordered proteins. Endogenous flexibility of L1-CT might play an important role in dynamic regulation of intracellular signaling: the ability of cytoplasmic tails to accommodate different targets has the potential to fine-tune signal transduction via cell surface receptors.

Original languageEnglish
Pages (from-to)4160-4168
Number of pages9
JournalBiochemistry
Volume47
Issue number13
DOIs
StatePublished - Apr 1 2008

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Computer aided manufacturing
Neurons
Binding Sites
Intrinsically Disordered Proteins
Ankyrins
Membranes
Signal transduction
Proteins
Ultracentrifugation
Cell Adhesion Molecules
Cell Surface Receptors
Neurology
Dynamic light scattering
Cytoplasmic and Nuclear Receptors
Endocytosis
Nervous System
Immunoglobulins
Signal Transduction
Glycoproteins
Magnetic Resonance Spectroscopy

ASJC Scopus subject areas

  • Biochemistry

Cite this

Characterization of the neuron-specific L1-CAM cytoplasmic tail : Naturally disordered in solution it exercises different binding modes for different adaptor proteins. / Tyukhtenko, Sergiy; Deshmukh, Lalit; Kumar, Vineet; Lary, Jeffrey; Cole, James; Lemmon, Vance; Vinogradova, Olga.

In: Biochemistry, Vol. 47, No. 13, 01.04.2008, p. 4160-4168.

Research output: Contribution to journalArticle

Tyukhtenko, Sergiy ; Deshmukh, Lalit ; Kumar, Vineet ; Lary, Jeffrey ; Cole, James ; Lemmon, Vance ; Vinogradova, Olga. / Characterization of the neuron-specific L1-CAM cytoplasmic tail : Naturally disordered in solution it exercises different binding modes for different adaptor proteins. In: Biochemistry. 2008 ; Vol. 47, No. 13. pp. 4160-4168.
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