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近日，美国哈佛医学院Alan Brown等研究人员合作发现，纤绒毛结构揭示富含羟脯氨酸的原生螺旋的O-连接糖基化密码。相关论文于2024年3月28日在线发表于国际学术期刊《细胞》。

研究人员表示，富含羟脯氨酸的糖蛋白（HRGP）是植物和藻类细胞外基质和细胞壁中无处不在的一类蛋白质，但人们对它们的原生结构或相互作用知之甚少。

研究人员使用电子冷冻显微镜（cryo-EM）确定了富含羟脯氨酸的纤绒毛结构，这是一种从藻类莱茵衣藻的纤毛中分离出来的细胞外丝。该结构表明，纤绒毛是由两个HRGP（一个MST1细丝包裹着一个MST3拷贝）形成的，这两个HRGP都具有超糖基化的聚（羟脯氨酸）螺旋。在螺旋内，羟脯氨酸残基的O-连接糖基化和穿插丝氨酸残基的O-半乳糖基化，形成了一个碳水化合物外壳。

对相关聚糖的分析揭示了羟脯氨酸的重复模式如何决定糖基化的类型和程度。MST3具有一个类似于PKD2的跨膜结构域，它与PKD2和SIP形成了一个异源的多囊蛋白样阳离子通道，从而解释了纤绒毛如何被系在纤毛膜上。

附：英文原文

Title: Mastigoneme structure reveals insights into the O-linked glycosylation code of native hydroxyproline-rich helices

Author: Jin Dai, Meisheng Ma, Qingwei Niu, Robyn J. Eisert, Xiangli Wang, Poulomi Das, Karl F. Lechtreck, Susan K. Dutcher, Rui Zhang, Alan Brown

Issue&Volume: 2024-03-28

Abstract: Hydroxyproline-rich glycoproteins (HRGPs) are a ubiquitous class of protein in the extracellular matrices and cell walls of plants and algae, yet little is known of their native structures or interactions. Here, we used electron cryomicroscopy (cryo-EM) to determine the structure of the hydroxyproline-rich mastigoneme, an extracellular filament isolated from the cilia of the alga Chlamydomonas reinhardtii. The structure demonstrates that mastigonemes are formed from two HRGPs (a filament of MST1 wrapped around a single copy of MST3) that both have hyperglycosylated poly(hydroxyproline) helices. Within the helices, O-linked glycosylation of the hydroxyproline residues and O-galactosylation of interspersed serine residues create a carbohydrate casing. Analysis of the associated glycans reveals how the pattern of hydroxyproline repetition determines the type and extent of glycosylation. MST3 possesses a PKD2-like transmembrane domain that forms a heteromeric polycystin-like cation channel with PKD2 and SIP, explaining how mastigonemes are tethered to ciliary membranes.

DOI: 10.1016/j.cell.2024.03.005

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00253-8