文摘
Saposin B is a water soluble -helical protein which can bind to membranes and extract selectedlipids, especially cerebroside sulfates. The X-ray structure of saposin B is homodimeric. There are twoconformations of the dimer in the crystal-one with a closed central cavity (the AB dimer) and one (theCD dimer) with a more open cavity. We have conducted a series of short (5 ns) molecular dynamicssimulations of saposin B, starting from both the AB and CD conformations and with/without bound lipidand/or water molecules within the central hydrophobic cavity. The more open (CD) dimer showed greaterconformational drift than the AB dimer. The conformational drift was also somewhat higher in the absenceof bound lipid. Two more extended (30 ns) simulations of AB and CD dimers were performed and analyzedin terms of changes in intersubunit packing within the dimers. The AB dimer remained largely unchangedin conformation over the duration of the extended simulation. In contrast, the CD dimer underwent asubstantial conformational change corresponding to a 'scissor' motion of the two monomers so as tocompress the central cavity to a more closed conformation than that seen in the AB dimer structure. AH-bond between the Q53 and Y54 side chains of the 3 helices of the two opposing monomers seems tohold the dimer in this 'scissor-closed' conformation. We suggest that a cycle of conformational changes,expanding and compressing the central cavity of the saposin B dimer, may play a key role in facilitatinglipid extraction from bilayers.