TY - JOUR
T1 - SAXS models of TGFBIp reveal a trimeric structure and show that the overall shape is not affected by the Arg124His mutation
AU - Basaiawmoit, R.V.
AU - Oliveira, C.L.P.
AU - Runager, K.
AU - Sørensen, C.S.
AU - Behrens, Manja Annette
AU - Jonsson, B.-H.
AU - Kristensen, T.
AU - Klintworth, G.K.
AU - Enghild, J.J.
AU - Pedersen, Jan Skov
AU - Otzen, Daniel Erik
N1 - MEDLINE® is the source for the MeSH terms of this document.
PY - 2011
Y1 - 2011
N2 - Human transforming growth factor β induced protein (TGFBIp) is composed of 683 residues, including an N-terminal cysteine-rich (EMI) domain, four homologous fasciclin domains, and an Arg-Gly-Asp (RGD) motif near the C-terminus. The protein is of interest because mutations in the TGFBI gene encoding TGFBIp lead to corneal dystrophy (CD), a condition where protein aggregates within the cornea compromise transparency. The complete three-dimensional structure of TGFBIp is not yet available, with the exception of a partial X-ray structure of the archetype FAS1 domain derived from Drosophila fasciclin-1. In this study, small-angle X-ray scattering (SAXS) models of intact wild-type (WT) human TGFBIp and a mutant (R124H) are presented. The mutation R124H leads to a variant of granular CD. The deduced structure of the TGFBIp monomer consists of four FAS1 domains in a simple "beads-on-a-string" arrangement, constructed by the superimposition of four consecutive Drosophila fasciclin domains. The SAXS-based model of the TGFBIp R124H mutant displayed no structural differences from WT. Both WT TGFBIp and the R124H mutant formed trimers at higher protein concentrations. The similar association properties and three-dimensional shape of the two proteins suggest that the mutation does not induce any major structural rearrangements, but points towards the role of other corneal-specific factors in the formation of corneal R124H deposits.
AB - Human transforming growth factor β induced protein (TGFBIp) is composed of 683 residues, including an N-terminal cysteine-rich (EMI) domain, four homologous fasciclin domains, and an Arg-Gly-Asp (RGD) motif near the C-terminus. The protein is of interest because mutations in the TGFBI gene encoding TGFBIp lead to corneal dystrophy (CD), a condition where protein aggregates within the cornea compromise transparency. The complete three-dimensional structure of TGFBIp is not yet available, with the exception of a partial X-ray structure of the archetype FAS1 domain derived from Drosophila fasciclin-1. In this study, small-angle X-ray scattering (SAXS) models of intact wild-type (WT) human TGFBIp and a mutant (R124H) are presented. The mutation R124H leads to a variant of granular CD. The deduced structure of the TGFBIp monomer consists of four FAS1 domains in a simple "beads-on-a-string" arrangement, constructed by the superimposition of four consecutive Drosophila fasciclin domains. The SAXS-based model of the TGFBIp R124H mutant displayed no structural differences from WT. Both WT TGFBIp and the R124H mutant formed trimers at higher protein concentrations. The similar association properties and three-dimensional shape of the two proteins suggest that the mutation does not induce any major structural rearrangements, but points towards the role of other corneal-specific factors in the formation of corneal R124H deposits.
UR - http://www.scopus.com/inward/record.url?scp=79953836704&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2011.02.052
DO - 10.1016/j.jmb.2011.02.052
M3 - Journal article
C2 - 21371477
AN - SCOPUS:79953836704
SN - 0022-2836
VL - 408
SP - 503
EP - 513
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 3
ER -