Premium
Three‐dimensional structure topology of the calreticulin P‐domain based on NMR assignment
Author(s) -
Ellgaard Lars,
Riek Roland,
Braun Daniel,
Herrmann Torsten,
Helenius Ari,
Wüthrich Kurt
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02382-6
Subject(s) - calreticulin , endoplasmic reticulum , topology (electrical circuits) , residue (chemistry) , sequence (biology) , nuclear overhauser effect , two dimensional nuclear magnetic resonance spectroscopy , crystallography , chemistry , peptide sequence , nuclear magnetic resonance spectroscopy , stereochemistry , biochemistry , mathematics , combinatorics , gene
Calreticulin (CRT) is an abundant molecular chaperone of the endoplasmic reticulum. Its central, proline‐rich P‐domain, comprising residues 189–288, contains three copies of each of two repeat sequences (types 1 and 2), which are arranged in a characteristic ‘111222’ pattern. Here we show that the three‐dimensional structure of CRT(189–288) contains a single hairpin fold formed by the entire polypeptide chain. The loop at the bottom of the hairpin consists of residues 227–247, and is closed by an anti‐parallel β‐sheet of residues 224–226 and 248–250. Two additional β‐sheets contain residues 207–209 and 262–264, and 190–192 and 276–278. The 17‐residue spacing of the β‐strands in the N‐terminal part of the hairpin and the 14‐residue spacing in the C‐terminal part reflect the length of the type 1 and type 2 sequence repeats. As a consequence of this topology the peptide segments separating the β‐strands in the N‐terminal part of the hairpin are likely to form bulges to accommodate the extra residues. These results are based on nearly complete sequence‐specific NMR assignments for CRT(189–288), which were obtained using standard NMR techniques with the 13 C/ 15 N‐labeled protein, and collection of nuclear Overhauser enhancement upper distance constraints.