doi:10.1016/j.jmb.2010.04.066
Communication
Horse Prion Protein NMR Structure and Comparisons with Related Variants of the Mouse Prion Protein
Daniel R. Pérez?, a, Fred F. Damberger?, a and Kurt Wüthrich, a, ,
a Institute of Molecular Biology and Biophysics, ETH Zurich, Schafmattstrasse 20, CH-8093 Zurich, Switzerland
Received 2 March 2010; revised 30 April 2010; accepted 30 April 2010. Edited by M. F. Summers. Available online 10 May 2010.
Abstract
The NMR structure of the horse (Equus caballus) cellular prion protein at 25 °C exhibits the typical PrPC [cellular form of prion protein (PrP)] global architecture, but in contrast to most other mammalian PrPCs, it contains a well-structured loop connecting the ß2 strand with the a2 helix. Comparison with designed variants of the mouse prion protein resulted in the identification of a single amino acid exchange within the loop, D167S, which correlates with the high structural order of this loop in the solution structure at 25 °C and is unique to the PrP sequences of equine species. The ß2-a2 loop and the a3 helix form a protein surface epitope that has been proposed to be the recognition area for a hypothetical chaperone, "protein X," which would promote conversion of PrPC into the disease-related scrapie form and thus mediate intermolecular interactions related to the transmission barrier for transmissible spongiform encephalopathies (TSEs) between different species. The present results are evaluated in light of recent indications from in vivo experiments that the local ß2-a2 loop structure affects the susceptibility of transgenic mice to TSEs and the fact that there are no reports on TSE in horses.
Keywords: cellular horse prion protein; transmissible spongiform encephalopathy; NMR structure determination; protein structure; ß2-a2 loop
Abbreviations: PrP, prion protein; PrPC, cellular form of PrP; PrPSc, scrapie form of PrP; ecPrP, horse PrP; mPrP, mouse PrP; TSE, transmissible spongiform encephalopathy; NOE, nuclear Overhauser enhancement; NOESY, NOE spectroscopy; ePrP, elk PrP; bvPrP, bank vole PrP
http://www.sciencedirect.com/
equine spongiform encephalopathy
THERE was a case of a horse with suspect Bovine Spongiform Encephalopathy and or another scrapie-like TSE, that was fed cattle cake. IN fact there were a report of similar cases in other horses, but as with the hounds with TSE, those studies were all ignored and finally just set aside due to all the other species going down with BSE. ...TSS
IN CONFIDENCE
SUSPECT BSE IN A HORSE
CYO BSE 1 9
IN CONFIDENCE
SUSPECT BSE IN A HORSE
The Parliamentary Secretary (Mr Maclean) will wish to be aware that, in making his differential diagnosis, a veterinary surgeon in the Reading area has included the possibility of BSE in a horse under his care. Although it is unlikely to be BSE, because of the symptoms exhibited the veterinarian believes that he cannot exclude the possibility. The case was brought to the notice of one of the veterinary staff at the CVL by the owner's veterinary surgeon and liaison is being maintained.
The horse in question is a five-year old eventing gelding which was purchased by the present owner about four months ago. Approximately two months after purchase the animal became a little apprehensive, developed mild nervous symptoms and became over-sensitive to noise. The nervous symptoms have increased and the horse is now practically impossible to ride. Investigations by the owner's private veterinary surgeon are continuing but it is likely that the animal will have to be destroyed.
If the horse should die or be destroyed, a full post-mortem examination will be required for insurance purposes and will probably be carried out at a non-Ministry laboratory. However, Mr Bradley of the Pathology Department, CVL, has informed the private veterinary surgeon that he is willing to provide a second opinion on the brain histology if requested.
I will keep the Parliamentary Secretary informed of any further developments in the case.
I CRAWFORD
14 May 1990
Mr M P H Hill, PS/Parliamentary secretary (Mr Maclean) - by FAX
cc:
Private Offices
Mr K C Meldrum
Mrs E A J Attridge D J Evans Mr K C Taylor Mr R Lawson Mr R Bradley. CVL
(hand written notes i cannot read all (cut short) as follows...tss)
The Parliamentary Secretary (Mr Maclean was grateful for this. He said that we must keep very close to ...on it, and when the horse dies, or is put down we must be told immediately. He also feels it is very important that our veterinary staff be involved in the brain examination. .........(cannot read the rest .............TSS)
90/05.14/10.1
http://collections.europarchive.org/tna/20080102214337/http://www.bseinquiry.gov.uk/files/yb/1990/05/14010001.pdf
1. Mr G S Podmore
PS/Secretary of State
cc PS/Permanent Secretary Mr .T W Preston Mr .T I Davies Mr D R Williams Mr D Summers
POSSIBLE SPONGIFORM ENCEPHALOPATHY IN A HORSE
You will wish to be aware that I have just received a note from Mr D Summers, the DRVO, that a possible case of a Spongiform Encephalopathy (SE) has been reported in a horse in the Brecon area.
The local veterinary surgeon reported yesterday afternoon a suspicion that a horse had contracted SE as it was showing clinical- symptoms similar to those described in cattle suffering from BSE. By yesterday evening the horse was in a comatose state and on humane grounds was destroyed by the veterinary surgeon.
At his request a full post mortem and a laboratory investigation will be started at the Carmarthen Veterinary Investigation Centre this morning in an attempt to ascertain the exact course. This will probably take at least 2 weeks. Charges to the veterinary surgeon have been waived in this instance.
Points particularly mentioned by the veterinary surgeon about this case were that the premises had an apparently similar case in another of their horses, several months ago; and that the horses had been fed cattle cake. Clearly. in his mind, there is a suspicion of a link with BSE; It must be emphasised. however, that at present we cannot even be certain that an SE of any sort is involved. These events are not exactly confidential but clearly no one is anxious to go out of their way to publicise them.
Any further information will be passed on as soon as it is available.
26th June 1990
ALUN HUWS WOAD2A
Note by The BSE Inquiry Secretariat The attached document may now be found at the following locations 90/06.26/10-1
90/06.26/9.1
http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1990/06/26009001.pdf
Mr A Huws Principal WOAD2A CP2
SUSPECT BSE IN A HORSE
You will wish to be aware that on Thursday afternoon 25 June the T/DVO Powys received a phone call from a veterinary Surgeon reporting his suspicion that a horse had contracted BSE after having been fed cattle cake. The clinical symptoms described were similar to those shown by cattle there being a similar case some months ago on the same premises.
The owner' s name and address is:
Irene Thomas J Thomas & Company Riding Stables Penybryn Llangorse Brecon
The horse is a 12 year old gelding used for pony trekking.
By yesterday evening the horse was in a comatose state and on humane grounds was destroyed by the veterinary Surgeon. At his request a full post mortem and laboratory investigation will be carried out at the Carmarthen Veterinary Investigation Centre this morning to ascertain the exact cause; I have been told this will take at least two weeks. Charges to the veterinary Surgeon have been waived in this instance.
I will inform you immediately I receive a diagnosis.
26 June 1990
D SUMMERS DRVO
cc
Mr D R Williams, RVO
Mr A R Hunter, SVIO
90/06.26/10.1
http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1990/06/26010001.pdf
Greetings,
PLEASE NOTE, TWO WEEKS, TWO MONTHS, TWO YEARS, TWO DECADES PASSED, AND NO OTHER MENTION OF THE CASE OF BSE TO HORSE WAS EVER MENTIONED AGAIN, that I could find. The above links were the last ever mentioned of these suspect cases of BSE in Horses, and the pathology reports there from were never furnished. SO, in my opinion, since the silence was so deafening, the BSE case to HORSE must have been positive, or they would have proudly displayed the pathology report negating the BSE positive in the Horse. ...TSS
PLEASE SEE FULL TEXT ;
Sunday, May 23, 2010
Horse Prion Protein NMR Structure and Comparisons with Related Variants of the Mouse Prion Protein
http://equinespongiformencephalopathy.blogspot.com/2010/05/horse-prion-protein-nmr-structure-and.html
TSS