Pellicena Patricia, Karow David S, Boon Elizabeth M, Marletta Michael A, Kuriyan John
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12854-9. doi: 10.1073/pnas.0405188101. Epub 2004 Aug 23.
Soluble guanylate cyclases are nitric oxide-responsive signaling proteins in which the nitric oxide sensor is a heme-binding domain of unknown structure that we have termed the heme-NO and oxygen binding (H-NOX) domain. H-NOX domains are also found in bacteria, either as isolated domains, or are fused through a membrane-spanning region to methyl-accepting chemotaxis proteins. We have determined the crystal structure of an oxygen-binding H-NOX domain of one such signaling protein from the obligate anaerobe Thermoanaerobacter tengcongensis at 1.77-angstroms resolution, revealing a protein fold unrelated to known structures. Particularly striking is the structure of the protoporphyrin IX group, which is distorted from planarity to an extent not seen before in protein-bound heme groups. Comparison of the structure of the H-NOX domain in two different crystal forms suggests a mechanism whereby alteration in the degree of distortion of the heme group is coupled to changes on the molecular surface of the H-NOX domain and potentially to changes in intermolecular interactions.
可溶性鸟苷酸环化酶是对一氧化氮有反应的信号蛋白，其中一氧化氮传感器是一个结构未知的血红素结合结构域，我们将其称为血红素-一氧化氮和氧结合（H-NOX）结构域。H-NOX结构域也存在于细菌中，要么作为孤立的结构域，要么通过跨膜区域与甲基接受趋化蛋白融合。我们已经确定了来自专性厌氧菌腾冲嗜热栖热菌的一种此类信号蛋白的氧结合H-NOX结构域的晶体结构，分辨率为1.77埃，揭示了一种与已知结构无关的蛋白质折叠。特别引人注目的是原卟啉IX基团的结构，它从平面性扭曲到了蛋白质结合血红素基团中前所未见的程度。两种不同晶体形式的H-NOX结构域结构的比较表明了一种机制，即血红素基团扭曲程度的改变与H-NOX结构域分子表面的变化以及潜在的分子间相互作用的变化相关联。
