Skip navigation
Please use this identifier to cite or link to this item: http://repository.iitr.ac.in/handle/123456789/26974
Title: Camel lactoferrin, a transferrin-cum-lactoferrin: Crystal structure of camel apolactoferrin at 2.6 Å resolution and structural basis of its dual role
Authors: Khan J.A.
Kumar, Pravindra R.Manish
Paramasivam M.
Yadav R.S.
Sahani M.S.
Sharma S.
Srinivasan A.
Singh T.P.
Published in: Journal of Molecular Biology
Abstract: Camel lactoferrin is the first protein from the transferrin superfamily that has been found to display the characteristic functions of iron binding and release of lactoferrin as well as transferrin simultaneously. It was remarkable to observe a wide pH demarcation in the release of iron from two lobes. It loses 50 % iron at pH 6.5 and the remaining 50 % iron is released only at pH values between 4.0 and 2.0. Furthermore, proteolytically generated N and C-lobes of camel lactoferrin showed that the C-lobe lost iron at pH 6.5, while the N-lobe lost it only at pH less than 4.0. In order to establish the structural basis of this striking observation, the purified camel apolactoferrin was crystallized. The crystals belong to monoclinic space group C2 with unit cell dimensions a = 175.8 Å, b = 80.9 Å, c = 56.4 Å, β = 92.4° and Z = 4. The structure has been determined by the molecular replacement method and refined to an R-factor of 0.198 (R-free = 0.268) using all the data in the resolution range of 20.0-2.6 Å. The overall structure of camel apolactoferrin folds into two lobes which contain four distinct domains. Both lobes adopt open conformations indicating wide distances between the iron binding residues in the native iron-free form of lactoferrin. The dispositions of various residues of the iron binding pocket of the N-lobe of camel apolactoferrin are similar to those of the N-lobe in human apolactoferrin, while the corresponding residues in the C-lobe show a striking similarity with those in the C-lobes of duck and hen apo-ovotransferrins. These observations indicate that the N-lobe of camel apolactoferrin is structurally very similar to the N-lobe of human apolactoferrin and the structure of the C-lobe of camel apolactoferrin matches closely with those of the hen and duck apo-ovotransferrins. These observations suggest that the iron binding and releasing behaviour of the N-lobe of camel lactoferrin is similar to that of the N-lobe of human lactoferrin, whereas that of the C-lobe resembles those of the C-lobes of duck and hen apo-ovotransferrins. Hence, it correlates with the observation of the N-lobe of camel lactoferrin losing iron at a low pH (4.0-2.0) as in other lactoferrins. On the other hand, the C-lobe of camel lactoferrin loses iron at higher pH (7.0-6.0) like transferrins suggesting its functional similarity to that of transferrins. Thus, camel lactoferrin can be termed as half lactoferrin and half transferrin. © 2001 Academic Press.
Citation: Journal of Molecular Biology, 309(3): 751-761
URI: https://doi.org/10.1006/jmbi.2001.4692
http://repository.iitr.ac.in/handle/123456789/26974
Issue Date: 2001
Publisher: Academic Press
Keywords: Camel apolactoferrin
Crystal structure
Lactoferrin
Transferrin
X-ray diffraction
ISSN: 222836
Author Scopus IDs: 57196726069
55064809000
6701391680
36913807600
7005205268
7405881718
7202314476
57218945130
Author Affiliations: Khan, J.A., Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India, National Research Centre On Camels, Bikaner, 334001, India
Kumar, P., Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India, National Research Centre On Camels, Bikaner, 334001, India
Paramasivam, M., Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India, National Research Centre On Camels, Bikaner, 334001, India
Yadav, R.S., Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India, National Research Centre On Camels, Bikaner, 334001, India
Sahani, M.S., Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India, National Research Centre On Camels, Bikaner, 334001, India
Sharma, S., Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India, National Research Centre On Camels, Bikaner, 334001, India
Srinivasan, A., Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India, National Research Centre On Camels, Bikaner, 334001, India
Singh, T.P., Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India, National Research Centre On Camels, Bikaner, 334001, India
Funding Details: 
Corresponding Author: Singh, T.P.; Department of Biophysics, , New Delhi 110029, India; email: tps@aiims.aiims.ac.in
Appears in Collections:Journal Publications [BT]

Files in This Item:
There are no files associated with this item.
Show full item record


Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.