General Information

Database accession: MF2100018

Name: Dimeric cytoplasmic domain of syndecan-4

PDB ID: 1ejp PDB

Experimental method: NMR

Assembly: homodimer

Source organism: Homo sapiens

Primer publication of the structure:

Shin J, Lee W, Lee D, Koo BK, Han I, Lim Y, Woods A, Couchman JR, Oh ES
Solution structure of the dimeric cytoplasmic domain of syndecan-4.
(2001) Biochemistry 40: 8471-8

PMID: 11456484 PubMed

Abstract:

The syndecans, transmembrane proteoglycans which are involved in the organization of cytoskeleton and/or actin microfilaments, have important roles as cell surface receptors during cell-cell and/or cell-matrix interactions. Since previous studies indicate that the function of the syndecan-4 cytoplasmic domain is dependent on its oligomeric status, the conformation of the syndecan-4 cytoplasmic domain itself is important in the understanding of its biological roles. Gel filtration results show that the syndecan-4 cytoplasmic domain (4L) itself forms a dimer stabilized by ionic interactions between peptides at physiological pH. Commensurately, the NMR structures demonstrate that syndecan-4L is a compact intertwined dimer with a symmetric clamp shape in the central variable V region with a root-mean-square deviation between backbone atom coordinates of 0.95 A for residues Leu(186)-Ala(195). The molecular surface of the 4L dimer is highly positively charged. In addition, no intersubunit NOEs in membrane proximal amino acid resides (C1 region) have been observed, demonstrating that the C1 region is mostly unstructured in the syndecan-4L dimer. Interestingly, two parallel strands of 4L form a cavity in the center of the dimeric twist similar to our previously reported 4V structure. The overall topology of the central variable region within the 4L structure is very similar to that of 4V complexed with the phosphatidylinositol 4,5-bisphosphate; however, the intersubunit interaction mode is affected by the presence of C1 and C2 regions. Therefore, we propose that although the 4V region in the full cytoplasmic domain has a tendency for strong peptide--peptide interaction, it may not be enough to overcome the repulsion of the C1 regions of syndecan-4L.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

fibronectin binding Interacting selectively and non-covalently with a fibronectin, a group of related adhesive glycoproteins of high molecular weight found on the surface of animal cells, connective tissue matrices, and in extracellular fluids. GeneOntology

thrombospondin receptor activity Combining with thrombospondin and transmitting the signal to initiate a change in cell activity. GeneOntology

protein kinase C binding Interacting selectively and non-covalently with protein kinase C. GeneOntology

Biological process:

regulation of fibroblast migration Any process that modulates the rate, frequency or extent of fibroblast cell migration. Fibroblast cell migration is accomplished by extension and retraction of a pseudopodium. GeneOntology

retinoid metabolic process The chemical reactions and pathways involving retinoids, any member of a class of isoprenoids that contain or are derived from four prenyl groups linked head-to-tail. Retinoids include retinol and retinal and structurally similar natural derivatives or synthetic compounds, but need not have vitamin A activity. GeneOntology

positive regulation of focal adhesion assembly Any process that activates or increases the frequency, rate or extent of focal adhesion assembly, the establishment and maturation of focal adhesions. GeneOntology

cell migration The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms. GeneOntology

inner ear receptor stereocilium organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a stereocilium. A stereocilium is an actin-based protrusion from the apical surface of inner ear receptor cells. GeneOntology

positive regulation of extracellular exosome assembly Any process that activates or increases the frequency, rate or extent of extracellular vesicular exosome assembly. GeneOntology

ureteric bud development The process whose specific outcome is the progression of the ureteric bud over time, from its formation to the mature structure. GeneOntology

positive regulation of exosomal secretion Any process that activates or increases the frequency, rate or extent of exosomal secretion. GeneOntology

positive regulation of stress fiber assembly Any process that activates or increases the frequency, rate or extent of the assembly of a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts. GeneOntology

glycosaminoglycan catabolic process The chemical reactions and pathways resulting in the breakdown of glycosaminoglycans, any one of a group of polysaccharides that contain amino sugars. GeneOntology

signal transduction The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell. GeneOntology

wound healing The series of events that restore integrity to a damaged tissue, following an injury. GeneOntology

neural tube closure The last step in the formation of the neural tube, where the paired neural folds are brought together and fuse at the dorsal midline. GeneOntology

positive regulation of protein kinase activity Any process that activates or increases the frequency, rate or extent of protein kinase activity. GeneOntology

glycosaminoglycan biosynthetic process The chemical reactions and pathways resulting in the formation of glycosaminoglycans, any of a group of polysaccharides that contain amino sugars. GeneOntology

Cellular component:

Golgi lumen The volume enclosed by the membranes of any cisterna or subcompartment of the Golgi apparatus, including the cis- and trans-Golgi networks. GeneOntology

integral component of plasma membrane The component of the plasma membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane. GeneOntology

lysosomal lumen The volume enclosed within the lysosomal membrane. GeneOntology

membrane raft Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions. GeneOntology

costamere Regular periodic sub membranous arrays of vinculin in skeletal and cardiac muscle cells, these arrays link Z-discs to the sarcolemma and are associated with links to extracellular matrix. GeneOntology

cell surface The external part of the cell wall and/or plasma membrane. GeneOntology

focal adhesion Small region on the surface of a cell that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. GeneOntology

extracellular exosome A membrane-bounded vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: A, B

Notes: No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.

Number of unique protein segments: 1

Chain A

Name: Syndecan-4

Source organism: Homo sapiens

Length: 28 residues

Sequence:Sequence according to PDB SEQRESRMKKKDEGSYDLGKKPIYKKAPTNEFYA

UniProtKB AC: P31431 (positions: 171-198) UniProt Coverage: 14.1%

UniRef90 AC: UniRef90_P31431 (positions: 171-198) UniRef90

Chain B

Name: Syndecan-4

Source organism: Homo sapiens

Length: 28 residues

Sequence:Sequence according to PDB SEQRESRMKKKDEGSYDLGKKPIYKKAPTNEFYA

UniProtKB AC: P31431 (positions: 171-198) UniProt Coverage: 14.1%

UniRef90 AC: UniRef90_P31431 (positions: 171-198) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Chain A:

The cytoplasmic domain of Syndecan-4 has been shown to adopt a stable structure upon binding to a partner protein (either through binding to an ordered domain PMID: 16533050 or through dimerization PMID: 11456484).

Chain B:

The cytoplasmic domain of Syndecan-4 has been shown to adopt a stable structure upon binding to a partner protein (either through binding to an ordered domain PMID: 16533050 or through dimerization PMID: 11456484).

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

There is 1 related structure in the Protein Data Bank:

• 1ejq

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