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 language | English |
|---|---|
| Pages (from-to) | 4160-4168 |
| Number of pages | 9 |
| Journal | Biochemistry |
| Volume | 47 |
| Issue number | 13 |
| DOIs | |
| State | Published - Apr 1 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Characterization of the neuron-specific L1-CAM cytoplasmic tail
T2 - Naturally disordered in solution it exercises different binding modes for different adaptor proteins
AU - Tyukhtenko, Sergiy
AU - Deshmukh, Lalit
AU - Kumar, Vineet
AU - Lary, Jeffrey
AU - Cole, James
AU - Lemmon, Vance
AU - Vinogradova, Olga
PY - 2008/4/1
Y1 - 2008/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=41449093695&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41449093695&partnerID=8YFLogxK
U2 - 10.1021/bi702433q
DO - 10.1021/bi702433q
M3 - Article
C2 - 18321067
AN - SCOPUS:41449093695
VL - 47
SP - 4160
EP - 4168
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 13
ER -