SAXS OF DRYSTROPHIN FRAGMENTS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 这些研究是NIH资助项目的一部分，该项目旨在确定结构域结构， 肌营养不良蛋白杆的生物物理特性，因其在杜氏肌营养不良中的作用而臭名昭著。 营养不良。SAXS将用于确定各种抗肌萎缩蛋白杆的结构 碎片，以确定其形状和灵活性;目的是确定杆区域， 包含破坏杆的铰链或扭结。杆状区域的基本构建块是血影蛋白型重复序列STR，其为存在于24个串联拷贝中的~100个氨基酸基序。STR折叠以形成锯齿形三螺旋α-螺旋束结构，其中三个α-螺旋呈锯齿形排列，其将多肽链的末端置于该束的相对末端。STR的串联排列因此产生长的杆状分子。 在某些区域，相邻的可疑交易反应形成相互作用的结构。这导致了嵌套模型的发展，其中STR束的三个螺旋不被认为是（ABC）（ABC）（ABC），而是A）B（CA）B（CA）B。在这个概念中，一个连续的，长CA螺旋交替与一半大小的，反平行的B螺旋在一个两步前进一步后退杆，和确切的生物物理域边界是不清楚的。虽然这两种模型曾经是竞争对手，但现在似乎两者都适用于棒的不同区域，可能导致非常不同的棒刚度。然而，从来没有任何直接测量杆的形状或刚度，这是我们研究的目的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. These studies are part of an NIH funded project to determine the domain structure and biophysical properties of the dystrophin rod infamous for its role in Duchenne Muscular Dystrophy. SAXS will be used to determine the structure of various dystrophin rod fragments to determine their shape and flexibility; the aim is to identify rod regions that contain hinges or kinks that disrupt the rod. The fundamental building block of the rod region is the spectrin type repeat, STR, an ~100 amino acid motif present in 24 tandem copies. STRs fold to form zigzag triple a-helical bundle structures with three a-helices in a zigzag arrangement that places the ends of the polypeptide chain at opposite ends of this bundle. Tandem arrangement of STRs thus produces a long, rod shaped molecule. In some regions, adjacent STRs form interacting structures. This has led to the development a of a nested model, in which the three helices of STR bundles are thought of not as (ABC)(ABC)(ABC) , but as A)B(CA)B(CA)B . In this conception, a continuous, long CA helix alternates with a half-size, antiparallel B helix in a two-steps-forward-one-step-back rod, and the exact biophysical domain boundaries are unclear. Although these two models were once rivals, it now seems that both may be applicable in different regions of the rod, possibly leading to very different rod rigidities. However, there is has never been any direct measurement of rod shape or rigidity, which is the aim of our studies.