The metal ion binding properties of calreticulin modulate its conformational flexibility and thermal stability.


Calreticulin (CRT) is a soluble chaperone involved in the conformational maturation of glycoproteins in the endoplasmic reticulum. Using biochemical and biophysical techniques including circular dichroism, proteolysis, and analytical ultracentrifugation, we have determined the effects of calcium and zinc ions on the structural properties of human CRT. Circular dichroism analysis has shown that the binding of calcium and zinc ions to CRT induces no significant changes in the secondary structure of the protein but affects in very distinct ways the local tertiary packing of these elements. More specifically, these studies have revealed that CRT adopts a more rigid and thermally stable structure upon binding calcium ions and a more loosely packed and thermally destabilized structure upon binding zinc ions. Consistent with these results, proteolysis experiments demonstrated that the intrinsic conformational flexibility of CRT can be modulated toward either a decrease or an increase in susceptibility to cleavage by chymotrypsin upon binding calcium or zinc ions, respectively. Results from sedimentation analysis indicated that the global three-dimensional structure of CRT is essentially unchanged upon binding calcium ions. In marked contrast, CRT self-associates reversibly to form dimers upon binding zinc ions. Collectively, our results provide evidence that calcium and zinc ions induce strikingly different changes in the biochemical and structural properties of CRT. Study holds ProTherm entries: 11764 Extra Details: additive : EDTA(2 mM), chaperone; structural properties; secondary structure; zinc ions

Submission Details

ID: bJYDcprG

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:43 p.m.

Version: 1

Publication Details
Li Z;Stafford WF;Bouvier M,Biochemistry (2001) The metal ion binding properties of calreticulin modulate its conformational flexibility and thermal stability. PMID:11551218
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 PDB Entries

Structure ID Release Date Resolution Structure Title
1JHN 2001-06-28T00:00:00+0000 2.9 Crystal Structure of the Lumenal Domain of Calnexin
1HHN 2000-12-22T00:00:00+0000 0 Calreticulin P-domain
1K91 2001-10-26T00:00:00+0000 0 Solution Structure of Calreticulin P-domain subdomain (residues 221-256)
1K9C 2001-10-29T00:00:00+0000 0 Solution Structure of Calreticulin P-domain subdomain (residues 189-261)
3O0V 2010-07-20T00:00:00+0000 2.3 Crystal structure of the calreticulin lectin domain
3O0W 2010-07-20T00:00:00+0000 1.95 Structural basis of carbohydrate recognition by calreticulin
3O0X 2010-07-20T00:00:00+0000 2.01 Structural basis of carbohydrate recognition by calreticulin
3RG0 2011-04-07T00:00:00+0000 2.57 Structural and functional relationships between the lectin and arm domains of calreticulin
3DOW 2008-07-07T00:00:00+0000 2.3 Complex structure of GABA type A receptor associated protein and its binding epitope on calreticulin

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
95.8 Calreticulin P15253 CALR_RABIT
95.0 Calreticulin P28491 CALR_PIG
95.3 Calreticulin P52193 CALR_BOVIN
95.3 Calreticulin P14211 CALR_MOUSE
95.3 Calreticulin P18418 CALR_RAT
95.8 Calreticulin Q8K3H7 CALR_CRIGR
99.7 Calreticulin Q2HWU3 CALR_MACFU
99.7 Calreticulin Q4R6K8 CALR_MACFA
99.7 Calreticulin Q4VIT5 CALR_CHLAE
100.0 Calreticulin P27797 CALR_HUMAN
96.4 Calnexin P35565 CALX_RAT
97.6 Calnexin P35564 CALX_MOUSE
96.1 Calnexin P27824 CALX_HUMAN
96.4 Calnexin Q5R440 CALX_PONAB
99.8 Calnexin P24643 CALX_CANLF