Karthigasan J, Inouye H, Kirschner D A
Children's Hospital, Boston, MA 02115, USA.
Med Hypotheses. 1995 Sep;45(3):235-40. doi: 10.1016/0306-9877(95)90111-6.
The minor myelin basic protein (MBP) isoforms with M(r) 21.5 and 17 kDa and the cytoskeletal proteins actin and tubulin are enriched in an interlamellar junctional specialization within central nervous system (CNS) myelin, the radial component (RC). To pursue the notion that there are specific interactions between these constituents, we searched for sequences in MBP that are homologous to sequences in the tubulin-binding protein tau. We found that the sequence motifs that are homologous to the phosphorylation and tubulin binding sites of tau (-RSP- and -KPGFG-) are also within the exon 2 and 6-encoded peptides of MBP. The -KPGFG- motif is unique to MBP when compared to other myelin proteins, and is highly conserved in the MBPs among vertebrate species. The physicochemical properties of the MBP and tau peptides that contain these sequences and their predicted secondary structures suggest that the peptides containing these motifs are hydrophilic and folded largely in turn and coil. This implies that the motifs are located at the protein surface where they would be accessible for interactions with other components of proteins or lipids. We propose that these putative phosphorylation and tubulin-binding sites in MBP may play functional roles in CNS myelin that are analogous to their roles in tau.
分子量为21.5 kDa和17 kDa的小分子髓鞘碱性蛋白（MBP）亚型以及细胞骨架蛋白肌动蛋白和微管蛋白，在中枢神经系统（CNS）髓鞘的层间连接特化结构即放射状成分（RC）中高度富集。为了探究这些成分之间存在特定相互作用的观点，我们在MBP中寻找与微管蛋白结合蛋白tau中的序列同源的序列。我们发现，与tau的磷酸化和微管蛋白结合位点（-RSP-和-KPGFG-）同源的序列基序也存在于MBP的外显子2和6编码的肽段中。与其他髓鞘蛋白相比，-KPGFG-基序是MBP所特有的，并且在脊椎动物物种的MBP中高度保守。包含这些序列的MBP和tau肽段的物理化学性质及其预测的二级结构表明，含有这些基序的肽段具有亲水性，并且大多呈反向折叠和卷曲。这意味着这些基序位于蛋白质表面，在那里它们可以与蛋白质或脂质的其他成分进行相互作用。我们提出，MBP中这些假定的磷酸化和微管蛋白结合位点在CNS髓鞘中可能发挥与它们在tau中类似的功能作用。
