Prohormonal cleavage sites are associated with omega loops.
Prohormonal cleavage sites are associated with omega loops.
复制标题
激素原裂解位点与 omega 环相关。
DOI：
10.1021/bi00453a024
复制
发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
Berry,R
中科院分区：
文献类型：
--
作者：
Bek,E;Berry,R
西北大学医学院细胞生物学和解剖学系，芝加哥，伊利诺斯州60611，1989年5月11日接收; 1989年8月14日接收修订的Mandarin pt摘要：分泌性肽是由较大的亲核蛋白或激素原，通过在由一个或多个碱性氨基酸组成的位点进行蛋白水解裂解而产生的。我们研究了这些切割位点与激素原中各种二级结构的关系。特别是，我们确定了切割位点与新定义的环类的关联。我们开发了一种算法，用于预测发生这种循环的前体的一级结构，并验证了这一过程的晶体学数据进行比较。当这种方法被应用于激素原，我们发现，约三分之一的裂解位点以前分配给反向转弯实际上是与环。此外，界定分泌肽的位点通常与环相关，并集中在环的颈部区域。这些数据可以用一个模型来解释，在这个模型中，加工内切蛋白酶与激素原上的两个位点相互作用：环中间的识别位点和环颈处的切割位点。在从其较大的前体产生分泌肽的过程中，肠溶加工起着重要的作用。已知裂解发生在赖氨酸和精氨酸残基上，最常见于Lys-Arg、Lys-Lys或Arg-Arg对，但也发生在f上。通信地址。单个残基或三个或四个碱性氨基酸的串（Gluschankof & Cohen，1987）。因此，蛋白质中切割位点的位置在其一级结构中被编码。然而，含有相同碱性氨基酸组的位点可以被差异性地切割，这表明切割位点周围区域的结构的某些方面决定了切割的动力学，实际上在某些情况下，
Department of Cell Biology and Anatomy, School of Medicine, Northwestern University, Chicago, Illinois 60611 Received May 11, 1989; Revised Manuscript Received August 14, 1989 abstract: Secretory peptides are generated from larger precursorproteins, or prohormones, by proteolytic cleavage at sites consisting of one or more basic amino acids. We have investigated the association of these cleavage sites with the various classes of secondary structurein the prohormones. In particular, we determined the association of cleavage sites with the newly defined category of loops. We developed an algorithm for predicting the occurrence of such loops from the primary structure of the precursor and validated this procedure by comparison to crystallographic data. When this method was applied to prohormones, we found that about one-third of the cleavage sites previously assigned to reverse turns were actually associated with loops. Moreover, sites that delimit secreted peptides are most often associated with loops and are concentrated in the neck regions of the loops. These data are interpreted interms of a model in which the processing endoprotease interactswith two sites on the prohormone: a recognition site in the middle of a loop and the cleavage site at its neck.^^^ oteolytic processing plays an essential role in the generation of secretory peptides fromtheir larger precursors. Cleavage is known to occur at lysine and arginine residues, most com-monly at a Lys-Arg, Lys-Lys, or Arg-Arg pair but also at f Supported by NIH Grant GM-35115.* To whom correspondence should be addressed. single residues or strings of three or four basic amino acids (Gluschankof & Cohen, 1987). Thus, the placement of cleavage sites in a protein is encoded in its primary structure. However, sites containing the same set of basic amino acids can be cleaved differentially, suggesting that some aspect of the structure of the region surrounding the cleavage site de-termines the kinetics of cleavage and, indeed in some cases,