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首页> 外文期刊>Acta crystallographica, Section D. Biological crystallography >Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH
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Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH

机译：组织解溶梭菌胶原酶ColG和ColH的三个多囊性肾病样结构域的结构

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摘要

Clostridium histolyticum collagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca2+-triggered domain reorientation to cause extensive tissue destruction. The collagenases consist of a collagenase module (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca2+-bound holo s2b (1.4 angstrom resolution, R = 15.0%, R-free = 19.1%) and holo s2a (1.9 angstrom resolution, R = 16.3%, R-free = 20.7%), as well as of Ca2+-free apo s2a (1.8 angstrom resolution, R = 20.7%, R-free = 27.2%) and two new forms of N-terminally truncated apo s2 (1.4 angstrom resolution, R = 16.9%, R-free = 21.2%; 1.6 angstrom resolution, R = 16.2%, R-free = 19.2%), are reported. The structurally similar PKD-like domains resemble the V-set Ig fold. In addition to a conserved beta-bulge, the PKD-like domains feature a second bulge that also changes the allegiance of the subsequent beta-strand. This beta-bulge and the genesis of a Ca2+ pocket in the archaeal PKD-like domain suggest a close kinship between bacterial and archaeal PKD-like domains. Different surface properties and indications of different dynamics suggest unique roles for the PKD-like domains in ColG and in ColH. Surface aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak interaction in the biphasic collagen-binding mode previously found in s2b-s3. B-factor analyses suggest that in the presence of Ca2+ the midsection of s2 becomes more flexible but the midsections of s2a and s2b stay rigid. The different surface properties and dynamics of the domains suggest that the PKD-like domains of M9B bacterial collagenase can be grouped into either a ColG subset or a ColH subset. The conserved properties of PKD-like domains in ColG and in ColH include Ca2+ binding. Conserved residues not only interact with Ca2+, but also position the Ca2+-interacting water molecule. Ca2+ aligns the N-terminal linker approximately parallel to the major axis of the domain. Ca2+ binding also increases stability against heat and guanidine hydrochloride, and may improve the longevity in the extracellular matrix. The results of this study will further assist in developing collagen-targeting vehicles for various signal molecules.
机译：组织溶梭菌胶原酶ColG和ColH是节段性酶，被Ca2 +触发的域重新定向激活，从而引起广泛的组织破坏。胶原酶由胶原酶模块（s1），可变数量的多囊肾病样（PKD-like）域（ColH中的s2a和s2b和ColG中的s2）和可变数量的胶原结合域（ColH中的s3）组成以及ColG中的s3a和s3b）。 Ca2 +结合的全息s2b（1.4埃分辨率，R = 15.0％，无R = 19.1％）和全息s2a（1.9埃分辨率，R = 16.3％，R-free = 20.7％）的X射线晶体结构，以及不含Ca2 +的载脂蛋白s2a（1.8埃分辨率，R = 20.7％，无R = 27.2％）和两种新形式的N末端截短的载脂蛋白s2（1.4埃分辨率，R = 16.9％，无R） ＝ 21.2％; 1.6埃分辨率，R ＝ 16.2％，无R ＝ 19.2％。结构相似的PKD样结构域类似于V-set Ig折叠。除了保守的β凸起以外，PKD样结构域还具有第二个凸起，该凸起也改变了随后的β链的效忠。这种β凸起和古细菌PKD样结构域中Ca2 +口袋的起源表明细菌和古细菌PKD样结构域之间的亲密关系。不同的表面性质和不同动力学的迹象表明，在ColG和ColH中，PKD样结构域具有独特的作用。在ColH s2a-s2b上发现的表面芳香族残基，而不是在ColG s2上发现，可能以先前在s2b-s3中发现的双相胶原结合模式提供弱的相互作用。 B因子分析表明，在存在Ca2 +的情况下，s2的中间部分变得更柔韧，但s2a和s2b的中间部分保持刚性。结构域的不同表面性质和动力学表明，M9B细菌胶原酶的PKD样结构域可以分为ColG子集或ColH子集。 ColG和ColH中PKD样结构域的保守性质包括Ca2 +结合。保守的残基不仅与Ca2 +相互作用，而且还定位与Ca2 +相互作用的水分子。 Ca2 +使N末端接头大致平行于域的主轴排列。 Ca2 +的结合还可以提高抗热和盐酸胍的稳定性，并可以改善细胞外基质的寿命。这项研究的结果将进一步帮助开发针对各种信号分子的胶原蛋白靶向载体。

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