Effect of linker segments on the stability of epithelial cadherin Domain 2.


Epithelial cadherin is a transmembrane protein that is essential in calcium-dependent cell-cell recognition and adhesion. It contains five independently folded globular domains in its extracellular region. Each domain has a seven-strand beta-sheet immunoglobulin fold. Short seven-residue peptide segments connect the globular domains and provide oxygens to chelate calcium ions at the interface between the domains (Nagar et al., Nature 1995;380:360-364). Recently, stability studies of ECAD2 (Prasad et al., Biochemistry 2004;43:8055-8066) were undertaken with the motivation that Domain 2 is a representative domain for this family of proteins. The definition of a domain boundary is somewhat arbitrary; hence, it was important to examine the effect of the adjoining linker regions that connect Domain 2 to the adjacent domains. Present studies employ temperature-denaturation and proteolytic susceptibility to provide insight into the impact of these linkers on Domain 2. The significant findings of our present study are threefold. First, the linker segments destabilize the core domain in the absence of calcium. Second, the destabilization due to addition of the linker segments can be partially reversed by the addition of calcium. Third, sodium chloride stabilizes all constructs. This result implies that electrostatic repulsion is a contributor to destabilization of the core domain by addition of the linkers. Thus, the context of Domain 2 within the whole molecule affects its thermodynamic characteristics. Study holds ProTherm entries: 22049, 22050, 22051, 22052, 22053, 22054, 22055, 22056, 22057, 22058, 22059, 22060, 22061, 22062, 22063, 22064 Extra Details: domain 2 (residues 107-212) thermodynamics; calcium binding; modular domains; circular dichroism; thermal denaturation

Submission Details

ID: qcysxasn3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:53 p.m.

Version: 1

Publication Details
Prasad A;Zhao H;Rutherford JM;Housley N;Nichols C;Pedigo S,Proteins (2006) Effect of linker segments on the stability of epithelial cadherin Domain 2. PMID:16287100
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Cadherin-2 P15116 CADH2_MOUSE
99.1 Cadherin-2 Q9Z1Y3 CADH2_RAT
98.1 Cadherin-2 B0KW95 CADH2_CALJA
98.1 Cadherin-2 P19022 CADH2_HUMAN
98.1 Cadherin-2 Q5R9X1 CADH2_PONAB
99.1 Cadherin-2 B4USZ0 CADH2_OTOGA
99.1 Cadherin-2 B2KI42 CADH2_RHIFE
99.1 Cadherin-2 P19534 CADH2_BOVIN
98.3 Cadherin-2 O55075 CADH2_CRIGR
95.4 Cadherin-2 P10288 CADH2_CHICK
90.7 Cadherin-2 P20310 CAD2B_XENLA