What function for human lithostathine?: structural investigations by three-dimensional structure modeling and high-resolution NMR spectroscopy.
Human lithostathine is a 144-residue protein, expressed in various organs and pathologies. Several biological functions have been proposed for this protein. Among others, inhibition of nucleation and growth of CaCO3 crystals in the pancreas and bacterial aggregation has retained attention, because lithostathine presents high sequence similarities with calcium-dependent (or C-type) lectins. To study its structure-function relationship and compare it with that of C-type lectins, we have built a model for lithostathine. This model is derived from the only two C-type lectins of known structures: rat mannose binding protein and human E-selectin. An original strategy, inspired by that proposed by Havel and Snow, was designed for model building. We have undertaken NMR studies on the natural protein. Although complete structure determination has not yet been achieved, the NMR studies did confirm the main characteristics of the model. From analysis of the proposed model, we concluded that lithostathine is not expected to present sugar- or calcium-binding properties. Therefore, the mechanisms of bacterial aggregation and inhibition of CaCO3 nucleation and growth have not yet been elucidated.
Patard
L
L
Laboratoire de RMN, URA 1308 du CNRS, DCSO, Ecole Polytechnique, Palaiseau, France.
Stoven
V
V
Gharib
B
B
Bontems
F
F
Lallemand
J Y
JY
De Reggi
M
M
D000595:Amino Acid Sequence; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000737:chemistry; D051847:Lithostathine; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D010182:Pancreatic Diseases; D010189:Pancreatic Juice / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D002135:Calcium-Binding Proteins; D037102:Lectins; D051847:Lithostathine; D009419:Nerve Tissue Proteins; C497617:REG1A protein, human