3RG0

Structural and functional relationships between the lectin and arm domains of calreticulin

Summary for 3RG0

• Entry DOI: 10.2210/pdb3rg0/pdb
• Descriptor: Calreticulin, CALCIUM ION (3 entities in total)
• Functional Keywords: beta-sandwich, chaperone, monoglucosylated proteins binding, carbohydrate binding, calcium binding, endoplasmic reticulum
• Biological source: Mus musculus (mouse); More
• Cellular location: Endoplasmic reticulum lumen : P14211
• Total number of polymer chains: 1
• Total formula weight: 38181.07

Authors

Kozlov, G.,Pocanschi, C.L.,Brockmeier, U.,Williams, D.B.,Gehring, K. (deposition date: 2011-04-07, release date: 2011-06-01, Last modification date: 2024-11-06)

Primary citation

Pocanschi, C.L.,Kozlov, G.,Brockmeier, U.,Brockmeier, A.,Williams, D.B.,Gehring, K.
Structural and Functional Relationships between the Lectin and Arm Domains of Calreticulin.
J.Biol.Chem., 286:27266-27277, 2011

PubMed Abstract: Calreticulin and calnexin are key components in maintaining the quality control of glycoprotein folding within the endoplasmic reticulum. Although their lectin function of binding monoglucosylated sugar moieties of glycoproteins is well documented, their chaperone activity in suppressing protein aggregation is less well understood. Here, we use a series of deletion mutants of calreticulin to demonstrate that its aggregation suppression function resides primarily within its lectin domain. Using hydrophobic peptides as substrate mimetics, we show that aggregation suppression is mediated through a single polypeptide binding site that exhibits a K(d) for peptides of 0.5-1 μM. This site is distinct from the oligosaccharide binding site and differs from previously identified sites of binding to thrombospondin and GABARAP (4-aminobutyrate type A receptor-associated protein). Although the arm domain of calreticulin was incapable of suppressing aggregation or binding hydrophobic peptides on its own, it did contribute to aggregation suppression in the context of the whole molecule. The high resolution x-ray crystal structure of calreticulin with a partially truncated arm domain reveals a marked difference in the relative orientations of the arm and lectin domains when compared with calnexin. Furthermore, a hydrophobic patch was detected on the arm domain that mediates crystal packing and may contribute to calreticulin chaperone function.

PubMed: 21652723
DOI: 10.1074/jbc.M111.258467

Experimental method

X-RAY DIFFRACTION (2.57 Å)