X-ray Characterization of Conformational Changes of Human Apo- and Holo-Transferrin

Campos-Escamilla, Camila; Siliqi, Dritan; Gonzalez-Ramirez, Luis A.; Lopez-Sanchez, Carmen; Gavira, Jose Antonio; Moreno, Abel

doi:10.3390/ijms222413392

Title: X-ray Characterization of Conformational Changes of Human Apo- and Holo-Transferrin

Journal Article · 12 December 2021 · International Journal of Molecular Sciences (Online)

DOI: https://doi.org/10.3390/ijms222413392 · OSTI ID:2469851

^[1];

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^[3]; Lopez-Sanchez, Carmen ^[3];

^[3];

^[4]

Universidad Nacional Autónoma de Mexico (Mexico)
National Research Council (CNR), Bari (Italy)
C.S.I.C. University of Granada (Spain)
Universidad Nacional Autónoma de Mexico (Mexico); C.S.I.C. University of Granada (Spain)

Human serum transferrin (Tf) is a bilobed glycoprotein whose function is to transport iron through receptor-mediated endocytosis. The mechanism for iron release is pH-dependent and involves conformational changes in the protein, thus making it an attractive system for possible biomedical applications. In this contribution, two powerful X-ray techniques, namely Macromolecular X-ray Crystallography (MX) and Small Angle X-ray Scattering (SAXS), were used to study the conformational changes of iron-free (apo) and iron-loaded (holo) transferrin in crystal and solution states, respectively, at three different pH values of physiological relevance. A crystallographic model of glycosylated apo-Tf was obtained at 3.0 Å resolution, which did not resolve further despite many efforts to improve crystal quality. In the solution, apo-Tf remained mostly globular in all the pH conditions tested; however, the co-existence of closed, partially open, and open conformations was observed for holo-Tf, which showed a more elongated and flexible shape overall.

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Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 2469851

Journal Information:: International Journal of Molecular Sciences (Online), Journal Name: International Journal of Molecular Sciences (Online) Journal Issue: 24 Vol. 22; ISSN 1422-0067

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology
Chemistry
Small-Angle X-ray Scattering
X-ray Crystallography
conformation change
human serum transferrin
pH-dependence

Title: X-ray Characterization of Conformational Changes of Human Apo- and Holo-Transferrin

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References (47)

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