药学学报

蛋白翻译后修饰与肿瘤免疫治疗

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金晶 , 季鸣 , 陈晓光 ^*

药学学报 | 综述 2019,54(10): 1711-1717

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药学学报 |综述 2019 , 54 (10) : 1711 -1717

蛋白翻译后修饰与肿瘤免疫治疗

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金晶, 季鸣, 陈晓光^*

作者信息

中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室/创新药物非临床药物代谢及PK/PD研究北京市重点实验室, 北京 100050

通讯作者:

*陈晓光, Tel:86-10-63165207, E-mail:chxg@imm.ac.cn

Post-translational modifications of proteins and cancer immunotherapy

Jing JIN, Ming JI, Xiao-guang CHEN^*

Affiliations

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines/Beijing Key Laboratory of Non-clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

出版时间: 2019-10-12 doi: 10.16438/j.0513-4870.2019-0695

文章导航

摘要

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蛋白翻译后修饰是一种蛋白功能调节的重要方式，对生理和病理条件下蛋白质的结构和功能都至关重要，且修饰种类繁多。肿瘤的免疫治疗是指通过激活体内的免疫细胞或使失能的免疫细胞正常化从而治疗肿瘤的有效方法。近年来研究发现，许多类型的蛋白翻译后修饰都参与了肿瘤微环境中免疫细胞的增殖、活化以及代谢重编程等过程，并可能影响肿瘤免疫治疗的疗效。因此，本文就几类不同蛋白翻译后修饰对肿瘤微环境中免疫细胞的作用进行综述，旨在为肿瘤免疫治疗提供新的思路。

关键词

蛋白翻译后修饰 / 肿瘤 / 肿瘤微环境 / 肿瘤免疫治疗

Abstract

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Post-translational modifications (PTMs) of proteins is an important mode of protein function regulation, which is essential for the structure and function of proteins under physiological and pathological conditions, and the types of modifications is wide. Cancer immunotherapy refers to an effective method for cancer treatment by activating or normalizing disabled immune cells. In recent years, researchers have found that many types of PTM are involved in the process of proliferation, activation and metabolic reprogramming of immune cells in cancer microenvironment, and may affect the efficacy of cancer immunotherapy. Therefore, this article reviews the effects of several different PTMs on immune cells in cancer microenvironment, and aims to provide new ideas for cancer immunotherapy.

Key words

post-translational modifications of proteins / cancer / cancer microenvironment / cancer immuno-therapy

引用本文

金晶, 季鸣, 陈晓光. 蛋白翻译后修饰与肿瘤免疫治疗. 药学学报, 2019 , 54 (10) : 1711 -1717 . DOI: 10.16438/j.0513-4870.2019-0695

Jing JIN, Ming JI, Xiao-guang CHEN. Post-translational modifications of proteins and cancer immunotherapy[J]. Acta Pharmaceutica Sinica, 2019 , 54 (10) : 1711 -1717 . DOI: 10.16438/j.0513-4870.2019-0695

正文

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肿瘤免疫治疗是指根据免疫学原理, 通过激活体内的免疫细胞或是失能的免疫细胞正常化从而增强机体的抗肿瘤免疫应答, 克服肿瘤的免疫逃逸, 抑制肿瘤恶性增殖的治疗方法。从1893年Coley发现术后化脓性链球菌感染能够意外地使肉瘤患者肿瘤消退, 到上世纪90年代Rosenberg使用白介素2 (interleukin 2, IL-2)及IL-2联用干扰素γ (interferon gamma, IFNγ)治疗转移性黑色素瘤, 直到2011年FDA批准首个细胞毒性T淋巴细胞抗原4 (cytotoxic T lymphocyte antigen 4, CTLA-4)抗体ipilimumab用于黑色素瘤治疗, 肿瘤的免疫疗法已经成为继手术、放疗和化疗之后的第四大疗法, 并被Science杂志评为了十大科学突破之首^{[1, 2]}。自用于治疗白血病的嵌合抗原受体T细胞免疫疗法(chimeric antigen receptor T-cell immunotherapy, CAR-T)以及用于实体肿瘤治疗的程序性死亡受体1/程序性死亡受体-配体1 (programmed cell death protein 1/programmed cell death-ligand 1, PD-1/PD-L1)抗体取得重大突破性进展后, 肿瘤免疫疗法愈发成为肿瘤治疗领域的研究热点。新的免疫哨卡及相应的抗肿瘤治疗药物被不断发现, 肿瘤治疗策略也从干预肿瘤细胞自身增殖侵袭的特性逐步转向针对肿瘤微环境中免疫细胞的类型、状态、表型转换以及能量代谢调解等。

蛋白质是组成生命体的重要物质, 也是生命活动的主要能量来源, 迄今发现, 人类细胞中约50%~90%的蛋白质都存在着不同类型的翻译后修饰, 蛋白翻译后修饰能够在生理及病理条件下, 通过影响蛋白的活性、稳定性、定位以及信号转导等, 快速调节细胞内的各种生命活动, 并扩大蛋白功能的多样性^[3-5], 如经典的磷酸化、泛素化、甲基化修饰, 以及非经典的糖基化、乙酰化、丙二酰化、琥珀酰化修饰等^[6]。近年来研究发现, 蛋白的翻译后修饰对免疫应答及免疫细胞信号调控具有非常重要的作用, 与免疫细胞的配体/受体、信号转导分子及功能蛋白的活化、转位、组装及代谢重编程等过程密切相关, 并可能影响肿瘤免疫治疗的疗效。因此, 本文就几类不同的蛋白翻译后修饰对肿瘤微环境中免疫细胞重要功能蛋白的影响及其对肿瘤免疫治疗的潜在作用做一综述。

1 蛋白糖基化与肿瘤免疫治疗

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糖基化是一种非常普遍的蛋白翻译后修饰方式, 通过糖基转移酶, 糖与多种蛋白质氨基酸残基结合形成糖苷键, 进而形成糖蛋白, 对蛋白质的折叠与稳定、细胞生长、受体活化、细胞黏附和免疫应答等方面都发挥了重要的调控作用^[7-9]。根据糖苷键的不同, 糖基化主要分为2种: O位糖基化和N位糖基化。O-乙酰氨基葡萄糖(O-GlcNAcylation)修饰是O位糖基化的一种, 目前研究发现O-GlcNAcylation修饰在肿瘤免疫治疗方面有重要作用, 与T/B淋巴细胞的增殖活化、中性粒细胞的活化以及单核巨噬细胞的功能密切相关^[10]。O-GlcNAcylation修饰是由Torres和Hart^[11]于1984年首次发现, 在糖代谢过程中, 葡萄糖可通过己糖胺合成通路(hexosamine biosynthesis pathway, HBP)合成UDP-N-乙酰基葡萄糖胺(uridine 5'-diphosphate-N-acetylglucosamine, UDP-GlcNAc), 进而被N-乙酰葡萄糖胺转移酶(O-GlcNAc transferase, OGT)作为底物进行蛋白质的O-GlcNAcylation。

肿瘤微环境中的T细胞大多处于能量耗竭状态, 失去了杀伤肿瘤的作用^[12]。因而如何使耗竭的T细胞正常化从而恢复功能已成为肿瘤免疫治疗最重要的一个突破口, 也是现有包括靶向PD1、PD-L1、淋巴细胞活化基因3 (lymphocyte-activation gene 3, LAG3)等肿瘤免疫治疗剂的作用基础。Swamy等^[13]发现相对初始T细胞, 激活的效应T细胞含有更多的O-GlcNAcylation修饰蛋白, T细胞在活化的重要阶段可通过葡萄糖的HBP介导蛋白的糖基化修饰, 从而介导细胞活化。此外OGT对胸腺中T祖细胞Notch介导的自我更新以及T细胞抗原受体(T cell receptor, TCR)激活的外周T细胞扩增至关重要。O-GlcNAcylation除了通过影响免疫细胞的活化对肿瘤免疫产生重要作用之外, 对肿瘤本身的抗原特性也发挥重要作用。目前, 针对肿瘤表面特异性抗原的治疗策略亦是肿瘤免疫治疗非常重要的思路和方法。Lavrsen等^[14]发现乳腺癌细胞表面黏蛋白1 (mucin 1, MUC1)异常的糖基化可成为特异性抗原作为免疫治疗的靶点。此外, 大量研究表明, 许多肿瘤都存在着O-GlcNAcylation的增加及关键酶的表达异常^[15]。O-GlcNAcylation直接参与调控肿瘤的增殖、凋亡、侵袭转移、血管生成以及代谢重编程。由此推测, 调控免疫细胞如T效应细胞或者直接调控肿瘤细胞的蛋白糖基化或可成为肿瘤免疫治疗的有效靶点。

2 蛋白泛素化修饰与肿瘤免疫治疗

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泛素化修饰是经典的翻译后修饰, 在生命活动中几乎无处不在。一个或者多个泛素分子在一系列酶作用下与底物蛋白质分子进行可逆的共价结合, 对靶蛋白进行修饰。被泛素化修饰的蛋白少数改变其定位、稳定与功能^[16], 多数通过泛素-蛋白酶体降解途径而降解, 从而在细胞的增殖、凋亡、转录^[17]、信号转导、损伤修复、免疫、肿瘤生成等生命活动中起到重要的调控作用^[18-20]。目前已发现3种泛素酶(E1、E2和E3)参与了泛素化修饰, 并且可由去泛素化酶(deubiquitinating proteins, DUBs)^[21]进行逆向调控。E3酶在泛素修饰途径中决定底物特异性, 目前约有600种, 通过与靶蛋白赖氨酸残基结合发挥作用。目前研究认为, E3泛素连接酶在机体的自身免疫和肿瘤免疫过程中起到了非常重要的作用^{[22, 23]}。

E3泛素连接酶cbl-b (casitas B-lineage lymphoma proto-oncogene b)是cbl蛋白家族的成员, 是T细胞中一个关键的免疫耐受因子, 与T细胞活化直接相关。研究表明, cbl-b缺陷小鼠能自发地排斥各种癌症^[24]。并且在缺乏共刺激的情况下, cbl-b缺陷的T细胞在抗原刺激下也会增殖并产生大量的IL-2^{[25, 26]}。Naramura等^[27]研究发现c-cbl敲除的T细胞在CD3刺激下反应性明显增强, 并发现cbl家族蛋白通过促进结合的TCR从细胞表面清除而负性调节T细胞活化, 对终止TCR信号有重要调控作用。cbl-b不仅对特异性免疫系统的T细胞活性有调节作用, 对固有免疫同样有重要影响。酪氨酸激酶受体tyro-3、axl和mertk在各种先天免疫细胞中发挥作用。Penninger团队^[28]发现cbl-b可通过与这几种酪氨酸激酶受体泛素化结合, 从而限制自然杀伤细胞(natural killer cell, NK)的功能。此外, 含有HECT (homologous to E6AP C terminus)结构域的E3连接酶Itch (E3 ubiquitin-protein ligase Itchy homolog)亦可通过影响下游转录因子jun-B (transcription factor jun-B, JUNB)的泛素化降解调控T细胞活化的信号转导通路, 进而影响辅助型T细胞2 (T helper 2 cell, Th2)的分化。敲除Itch可以使T细胞的活化与增殖能力明显增强^[29]。淋巴细胞蛋白中与无效能相关的基因(gene related to anergy in lymphocytes protein, Grail)作为一种E3连接酶在活化异常的T细胞中高表达, 通过促进CD3的泛素化降解从而限制TCR激活介导的免疫应答^{[30, 31]}。有研究表明, 在人结直肠癌和小鼠结直肠癌模型中, Ⅰ型干扰素受体(interferon alpha/beta receptor 1, IFNAR1)处于下调状态, 这是导致肿瘤微环境中细胞毒性T细胞免疫耐受的重要原因^[32]。E3泛素连接酶SCFHOS通过泛素化修饰IFNAR1使其降解, 并介导Ⅰ型IFN下调, 从而限制T细胞的活性和功能, 促进肿瘤生长^[33]。另外, 陈兰芬课题组^[34]研究发现, 转录辅助因子(transcriptional coactivator with PDZ-binding motif, TAZ)不仅可作为辅助性T细胞17 (T helper cell 17, Th17)分化决定性转录因子(nuclear receptor ROR-gamma, RORγt)共刺激转录因子促进Th17表达, 还可以介导RNA结合蛋白fox-1同源物3 (RNA binding protein fox-1 homolog 3, Fox3)通过泛素化-蛋白酶体途径降解, 抑制T细胞向调节性T细胞(regulatory T cells, Treg)的分化, 从而增强机体的免疫应答, 减轻肿瘤微环境的免疫抑制。

免疫哨卡及其抑制剂的寻找是目前肿瘤免疫治疗领域最热的研究方向之一^{[35, 36]}。有研究表明, 在活化的T细胞中, PD-1的表达受到E3连接酶F盒蛋白38 (F-box only protein 38, Fbxo38)的调控, 经由泛素化-蛋白酶体途径降解^[37]。条件性敲除小鼠T细胞Fbxo38可通过提高肿瘤浸润T细胞内PD-1的水平从而促进肿瘤生长, 而通过IL-2刺激上调Fbxo38的转录, 可降低T细胞中PD-1的表达水平, 增强其抗肿瘤活性。此外, E3泛素连接酶cbl-b缺失亦能够导致T细胞和NK细胞对PD-1介导的免疫耐受调节不敏感^{[38, 39]}。

E3泛素连接酶不仅调节免疫细胞的活性与功能, 对肿瘤细胞本身和肿瘤微环境也有重要的调节作用。多种肿瘤细胞都存在E3连接酶失调^{[40, 41]}。研究发现, 肿瘤抑制因子早幼粒细胞白血病蛋白(promyelocytic leukemia protein, PML)对肿瘤的侵袭和迁移有负向调节作用。PML水平降低还能通过上调CD73、尿激酶型纤溶酶原激活物受体(urokinase plasminogen activator surface receptor, UPAR)和血清淀粉样蛋白A2 (serum amyloid A-2 protein, SAA2), 增加肿瘤微环境中Treg细胞和M2巨噬细胞的数量, 同时降低CD8⁺ T细胞的数量, 达到免疫抑制作用。在肺癌中, 泛素连接酶CRL4WDR4泛素化降解PML, 通过促进肿瘤微环境的免疫抑制促进肺癌的进展^[42]。因此, 通过对与免疫调节相关的E3泛素化连接酶或其底物蛋白进行靶向调控可能为肿瘤免疫治疗提供新的机会。

NF-κB在机体的炎症免疫反应中发挥重要作用。细胞在静息状态时, NF-κB被IκB家族蛋白复合物“禁锢”在胞浆, NF-κB核定位信号(nuclear localization signal, NLS)被阻断。在对外部刺激的反应中, IκB迅速以泛素依赖性的方式被降解, 释放NF-κB入核, 激活信号转导与下游基因转录^[43]。有研究发现, B细胞内的去泛素化酶Otud7b可以特异性调控非经典NF-κB信号通路, 介导B细胞的成熟与活化^{[44, 45]}。Otud7b亦在TCR信号通路转导中发挥关键作用, 可通过去泛素化TCR信号通路的酪氨酸激酶Zap70, 调节T细胞的活化和分化^[46]。由此推测, 调节相关蛋白的泛素化修饰过程可能成为肿瘤免疫治疗的有效手段。

3 蛋白乙酰化修饰与肿瘤免疫治疗

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赖氨酸乙酰化的发现可追溯至1964年, 是一种可逆的PTM, 通常由两类酶调控, 赖氨酸乙酰化酶(lysine acetyltransferase, KAT)和赖氨酸去乙酰化酶(lysine deacetyltransferase, KDAT), 由于乙酰化修饰最早在组蛋白上被发现, 也常称作组蛋白乙酰化酶(histone acetyltransferase, HAT)和组蛋白去乙酰化酶(histone deacetylase, HDAC)^[47]。它们分别在核内或胞内发挥各自的功能, 如转录调节和参与代谢, 研究表明乙酰化的平衡在细胞生长、年龄衰老和癌症等疾病发生的过程中发挥关键作用^{[48, 49]}。在肿瘤发生过程中, HAT和HDAC都可能发生突变, 导致原癌基因和抑癌基因的异常表达^{[50, 51]}。因此, HDAC抑制剂也被开发用于癌症治疗, 自2006年伏立诺他(vorinostat)被批准用于T细胞淋巴瘤后, 后续又有3个HDAC抑制剂—罗米地辛、贝利司他和帕比司他被FDA批准用于癌症治疗^[52]。

蛋白赖氨酸残基的乙酰化可调节许多蛋白的结构和功能, 组蛋白的乙酰化可对染色质重塑并激活多种基因转录。HDAC抑制剂除了能够直接抑制肿瘤生长, 其引发的肿瘤细胞死亡尚能够激活免疫系统, 引发强烈的肿瘤免疫反应。Khan等^[53]发现经HDAC抑制剂处理的黑色素瘤细胞上主要组织相容性复合体Ⅱ (major histocompatibility complex Ⅱ, MHC Ⅱ)、CD40和活化B7-1/2抗原(activation B7-1/2 antigen, B7-1/2)的表达显著增加从而提升抗原提呈能力。另一方面, 高迁移率族蛋白B1 (high mobility group protein B1, HMGB1)可促进树突状细胞(dendritic cell, DC)成熟, 致敏T细胞^[54]。正常凋亡情况下, HMGB1是与染色质紧密结合的, 但Bonaldi等^[55]发现, 在乙酰化状态下, HMGB1可从凋亡的细胞中释放, 协同其他促炎因子引发更加强烈的免疫反应, 在肿瘤凋亡基础上更有效地杀伤肿瘤。此外, Finn^[56]亦提出乙酰化的蛋白与过表达或错误折叠等原因产生的肿瘤相关抗原相似, 也可作为抗原激活免疫反应。NK细胞可通过其表面活化的Ⅱ型完整膜蛋白(NKG2-D type Ⅱ integral membrane protein, NKG2D)识别并杀伤肿瘤细胞, HDAC抑制剂可提高包括视黄酸-早期诱导型克隆-1 (retinoic acid-early-inducible clone-1, RAE-1)在内的肿瘤细胞NKG2D配体的表达量^[57]。López-Soto等^[58]发现Ⅰ型HDAC在肿瘤中的表达增加(即肿瘤内蛋白乙酰化水平降低), 会减少肿瘤NKG2D配体的表达并抑制NK细胞对肿瘤的免疫反应。除HDAC抑制剂外, HAT抑制剂也对肿瘤免疫治疗有一定的影响。FOXP3是对Treg细胞生长发挥重要功能的转录调节因子, 其活性主要受乙酰化调节, 乙酰化能使其与染色质结合能力增强, 从而增加Treg细胞的数量和活性^[59]。经HDAC抑制剂治疗的小鼠体内, Treg细胞数量和免疫抑制功能均有增加, 抑制免疫系统的抗肿瘤效应^[60]。因此, 小分子HAT抑制剂能够下调Treg活性, 达到增强肿瘤免疫治疗的目的。此外, 在代谢相关酶中, 乙酰化也常常发挥开/关的作用, 因此肿瘤的发生也常常与代谢酶乙酰化异常相关^[61]。例如, 烯醇化酶α (α-enolase, ENOA)是丙酮酸合成过程中的代谢酶, 在白血病和宫颈癌等多种癌症细胞中, ENOA的乙酰化会高于正常水平^[62]。

4 蛋白丙二酰化修饰与肿瘤免疫治疗

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丙二酰化是最近发现的一种蛋白翻译后修饰, 以丙二酰辅酶A作为底物, 使赖氨酸发生丙二酰化, 从而影响蛋白构成以及与靶蛋白的结合^{[63, 64]}。它与脂肪酸合成及氧化、线粒体呼吸、糖酵解和组蛋白的修饰密切相关^[65]。然而目前人们对蛋白丙二酰化后的具体作用仍知之甚少。巨噬细胞作为固有免疫的第一道防线, 也是组成肿瘤免疫微环境中的重要细胞。传统分类方法可以将其分为促炎的M1型(表达一氧化氮合酶)以及抑炎的M2型(表达精氨酸酶Ⅰ)巨噬细胞。M1型巨噬细胞能够产生大量肿瘤坏死因子-α (tumor necrosis factor α, TNFα)等炎症因子, 有助于抗肿瘤治疗, 而M2型巨噬细胞主要分泌白介素-10 (interleukin-10, IL-10)等抑炎因子, 不但能够造成肿瘤微环境的免疫抑制状态而且能够促进肿瘤的侵袭转移。大量研究表明, 肿瘤相关的巨噬细胞(tumor-associated macrophages, TAM)基本为M2表型^{[66, 67]}。因此, 促进肿瘤微环境中M2向M1极化, 使更多的M0向M1转化已经成为了抗肿瘤免疫治疗的一个重要方向。Galván-Peña等^[68]研究发现, 静息期巨噬细胞内的甘油醛-3-磷酸脱氢酶(glyceraldehyde-3-phosphate dehydrogenase, GAPDH), 通常能够结合于许多包括TNFα在内的炎症相关mRNA上, 从而抑制其翻译。而在脂多糖(lipopolysaccharide, LPS)刺激下, GAPDH的第213位赖氨酸会发生丙二酰化, 致使其从这些mRNA上解离, 促进这些炎症相关mRNA的翻译, 进一步产生TNFα和IL-1β等促炎因子, 使M0巨噬细胞向M1型转化。由此推测, 调控这种保守蛋白的丙二酰化, 能够通过调节巨噬细胞炎症因子的产生及表型改变, 从而有助于肿瘤免疫治疗。

5 蛋白琥珀酰化修饰与肿瘤免疫治疗

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蛋白琥珀酰化也是近年来新发现的一类蛋白翻译后修饰, 影响众多细胞功能, 并与蛋白乙酰化相关^[69]。琥珀酸作为三羧酸循环重要的中间产物, 不但参与线粒体ATP的产生、细胞能量代谢, 还能通过调节低氧诱导因子-1α (hypoxia inducible factor-1α, HIF-1α)参与炎症及肿瘤信号转导途径^[70-72]。琥珀酸对肿瘤免疫治疗中M1型巨噬细胞、DC细胞及T细胞, 都具有重要的功能调节作用^{[72, 73]}。研究表明, 大部分肿瘤中都存在琥珀酸脱氢酶(succinate dehydrogenase, SDH)的突变^[74], 而SDH突变导致的琥珀酸堆积及蛋白赖氨酸的琥珀酰化, 可能是促进肿瘤发展的重要因素^[75]。近年来研究发现, 肉碱脂酰转移酶1A (carnitine palmityltransferase-1A, CTP1A)介导的S100A10蛋白第47位赖氨酸的琥珀酰化能够增加胃癌的侵袭转移^[76]。乳腺癌的进展也与肿瘤细胞内的琥珀酰化密切相关^[77]。组蛋白的翻译后修饰对DNA损伤修复及肿瘤免疫治疗起到重要作用, 最近研究表明, 组蛋白亦能够被琥珀酰化修饰^{[78, 79]}, 而其修饰后对肿瘤及肿瘤免疫治疗的影响仍有待进一步研究。

6 小结与展望

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蛋白翻译后修饰的类型众多并在免疫反应中扮演重要角色, 尽管目前诸如泛素化和糖基化等PTM已越来越多地被证实与肿瘤微环境中各类免疫细胞的功能相关, 但其他类型的PTM (如乙酰化、琥珀酰化、丙二酰化、棕榈酰化、巴豆酰化等)在肿瘤免疫中的作用依然知之甚少, 同时是否存在其他PTM类型并会对肿瘤免疫治疗产生潜在影响也仍然未知, 需要未来更加深入地研究。此外, PTM除了能够调节包括免疫哨卡PD1等现有成熟的肿瘤免疫治疗靶点, PTM对肿瘤细胞和免疫细胞自身代谢重编程的关键酶也有重要的调控作用, 不仅可以影响肿瘤细胞自身的能量代谢, 并且会改变肿瘤微环境中免疫细胞的代谢重编程从而影响整个肿瘤微环境。因此, 针对这些PTM中关键蛋白/酶的发现及相应激动剂/抑制剂的寻找, 肿瘤免疫治疗乃至肿瘤免疫微环境中的细胞代谢治疗, 将会成为未来肿瘤治疗的重要研究方向。

基金

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“十三五”国家“重大新药创制”科技重大专项(2018ZX09711001-003)

参考文献

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2019年第54卷第10期

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doi: 10.16438/j.0513-4870.2019-0695

接收时间：2019-08-29
首发时间：2026-01-26
出版时间：2019-10-12

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收稿日期：2019-08-29
修回日期：2019-09-05

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“十三五”国家“重大新药创制”科技重大专项(2018ZX09711001-003)

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*陈晓光, Tel:86-10-63165207, E-mail:chxg@imm.ac.cn

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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