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A bacteriophage tubulin forms microtubule-like assemblies with nine protofilaments. 一个噬菌体微管蛋白形成有9根原丝的微管状集合。

IF 4.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure

Pub Date : 2025-12-29 DOI: 10.1016/j.str.2025.12.002

Dwaipayan Basu, Siyu Chen, Ying-Xing Li, Niklas Klusch, Koe Inlow, Joe Pogliano, Elizabeth Villa, Kevin D Corbett

Tubulin family proteins play central roles in the organization and dynamics of cytoskeletal systems across the Tree of Life. In one family of bacteriophages (phages), tubulin-like proteins called PhuZ (Phage tubulin/FtsZ) form dynamic filaments that position and rotate an intracellular compartment, the "phage nucleus," in which the phage genome is replicated. PhuZ filaments also mediate trafficking of nascent capsids from the cell periphery to the phage nucleus for genome packaging. PhuZ from the Pseudomonas-infecting phages 201Phi2-1 and PhiKZ form assemblies with three protofilaments. Here, we determine a 2.8 Å resolution structure of PhuZ from the E. coli-infecting phage Goslar, which forms an elaborate "cytoskeletal vortex" in infected cells. We find that in vitro-assembled Goslar PhuZ forms rigid tubes with nine nearly-straight protofilaments. The lateral interactions mediating this assembly are fundamentally different from eukaryotic tubulin, leading to a distinctive overall architecture for Goslar PhuZ filaments.

微管蛋白家族蛋白在整个生命之树的细胞骨架系统的组织和动力学中起着核心作用。在一个噬菌体家族中，称为PhuZ（噬菌体微管蛋白/FtsZ）的微管蛋白样蛋白形成动态细丝，定位和旋转细胞内隔室，即“噬菌体核”，噬菌体基因组在其中复制。PhuZ丝也介导新生衣壳从细胞外围到噬菌体细胞核的运输，以进行基因组包装。来自假单胞菌感染噬菌体201Phi2-1的PhuZ和PhiKZ形成具有三个原丝的组装体。在这里，我们从大肠杆菌感染的噬菌体Goslar中确定了2.8 Å分辨率的PhuZ结构，它在感染细胞中形成了一个精心设计的“细胞骨架漩涡”。我们发现在体外组装的Goslar PhuZ形成具有9个几乎直的原丝的刚性管。介导这种组装的横向相互作用与真核微管蛋白根本不同，这导致Goslar PhuZ细丝具有独特的整体结构。

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引用次数: 0

Mechanism of SHP2 activation by bis-Tyr-phosphorylated Gab1. 双- tyr1磷酸化Gab1激活SHP2的机制。

IF 4.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure

Pub Date : 2025-12-22 DOI: 10.1016/j.str.2025.11.018

Lisa Machner, Alaa Shaikhqasem, Tobias Gruber, Farzad Hamdi, Constanze Breithaupt, Judith Kniest, Felix Wiebe, Marc Lewitzky, Christoph Parthier, Fotis L Kyrilis, Jochen Balbach, Panagiotis L Kastritis, Stephan M Feller, Milton T Stubbs

The non-receptor tyrosine phosphatase SHP2 (SH2 domain-containing protein tyrosine phosphatase 2) (PTPN11) is a regulator of diverse cellular functions including mitogenic activation and cell migration. It comprises two tandem Src-homology 2 (SH2) domains followed by the catalytic domain and is autoinhibited by the N-terminal SH2 domain blocking access to the active site. Mutations influencing auto-inhibition have been implicated in cancer and other diseases, and allosteric inhibitors have been developed that stabilize the inactive state. Here, we show that the intrinsically disordered bis-phosphorylated SHP2-activating peptide pY⁶²⁷pY⁶⁵⁹-Gab1 binds to both SH2 domains, undergoing partial ordering in the process. In addition to eliciting changes in SH2 domain dynamics, the peptide reorganizes their relative orientations to generate a new SH2-SH2 interface. Our data suggest an active conformation for SHP2 that is also applicable to the hematopoietic cell-specific SHP1 (PTPN6), shedding light on the activation mechanism of both enzymes and paving the way for the development of novel compounds to modulate SHP2 activity.

非受体酪氨酸磷酸酶SHP2（含SH2结构域蛋白酪氨酸磷酸酶2）（PTPN11）是多种细胞功能的调节剂，包括有丝分裂激活和细胞迁移。它由两个串联的Src-homology 2 （SH2）结构域和催化结构域组成，并受到n端SH2结构域的自动抑制，阻止进入活性位点。影响自身抑制的突变与癌症和其他疾病有关，而变构抑制剂已被开发出来以稳定非活性状态。在这里，我们发现内在无序的双磷酸化shp2激活肽pY627pY659-Gab1结合到SH2的两个结构域，在这个过程中经历了部分排序。除了引起SH2结构域动力学的变化外，肽重组它们的相对方向以产生新的SH2-SH2界面。我们的数据表明，SHP2的活性构象也适用于造血细胞特异性SHP1 (PTPN6)，揭示了这两种酶的激活机制，并为开发调节SHP2活性的新化合物铺平了道路。

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引用次数: 0

The impact of N-glycan conformational entropy on the binding affinity of Fc γ receptor IIIa/CD16a n -聚糖构象熵对Fc γ受体IIIa/CD16a结合亲和力的影响