| | |  | | | | Record from Web of Science® | | | | | | |
| CHARACTERIZATION AND STRUCTURAL-ANALYSIS OF A FUNCTIONAL HUMAN SERUM TRANSFERRIN VARIANT AND IMPLICATIONS FOR RECEPTOR RECOGNITION |
|
|
| Author(s): EVANS RW, CRAWLEY JB, GARRATT RC, GROSSMANN JG, NEU M, AITKEN A, PATEL KJ, MEILAK A, WONG C, SINGH J, BOMFORD A, HASNAIN SS |
| Source: BIOCHEMISTRY Volume: 33 Issue: 41 Pages: 12512-12520 Published: OCT 18 1994 |
| Times Cited: 21 References: 50 |
| Abstract: The nucleotide and amino acid substitutions leading to the only known functional variant of human serum transferrin have been characterized by sequencing of a peptide produced by cyanogen bromide digestion and genomic PCR coupled with cycle sequencing, respectively. There is an amino acid substitution at position 394 (Gly --> Arg) resulting from a mutational transition, G --> A, in the first nucleotide of the codon GGG. The Zn2+-, Al3+-, and Cu2+-binding properties of the variant, ascertained by UV difference spectra and, in the case of copper, protein fluorescence quenching, confirm that these metals bind to only one of the two sites. Solution X-ray scattering measurements indicate that the lobe (the C-lobe) containing the mutation remains ''open'' in the iron-bound state, and modeling studies suggest that this is a consequence of the formation of a salt bridge between Arg394 in the variant protein and Asp392, one of the iron-binding ligands in the C-lobe. This rationalizes for the first time the observed reduction in receptor affinity of the diferric variant protein for PHA-stimulated lymphocytes [Young, S. P., et al. (1984) Br. J. Haematol. 56, 581-587] and here repeated with K562 cells. These data lend support to the hypothesis that the closed conformation for both lobes contributes to receptor recognition. |
| Document Type: Article |
| Language: English |
| Reprint Address: EVANS, RW (reprint author), UNITED MED & DENT SCH, GUYS HOSP, DIV BIOCHEM & MOLEC BIOL, LONDON SE1 9RT, ENGLAND |
Addresses:
1. SERC, DARESBURY LAB, MOLEC BIOPHYS GRP, WARRINGTON WA4 4AD, CHESHIRE ENGLAND
2. NATL INST MED RES, PROT STRUCT LAB, LONDON NW7 1AA, ENGLAND
3. UNIV LONDON KINGS COLL, SCH MED & DENT, INST LIVER STUDIES, LONDON SE5 9PJ, ENGLAND
4. UNIV SAO PAULO, INST FIS SAO CARLOS, BR-13560 SAO CARLOS, BRAZIL
5. WARNER LAMBERT PARKE DAVIS, PARKE DAVIS PHARMACEUT RES, ANN ARBOR, MI 48105 USA |
| Publisher: AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: PM582 |
| ISSN: 0006-2960 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |