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The Role of Aspartic Proteases in Plant–Pathogen Interactions

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The Role of Aspartic Proteases in Plant–Pathogen Interactions biology Review Defense and Offense Strategies: The Role of Aspartic Proteases in Plant–Pathogen Interactions Laura Figueiredo , Rita B. Santos *,† and Andreia Figueiredo † Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal; lafi[email protected] (L.F.); aafi[email protected] (A.F.) * Correspondence: [email protected]; Tel.: +351-217-522-448 † These senior authors contributed to this work equally. Simple Summary: Plants are sessile organisms that are continuously exposed to adverse environmen- tal factors, both abiotic and biotic. Plant immunity is an intricate system that involves a remarkable array of structural, chemical, and protein-based layers of defense, aiming to stop pathogens before they cause irreversible damages. Proteases are an integral part of plant defense systems, with several hubs of action, from pathogen recognition and priming to the activation of plant hypersensitive response. Within this wide group of proteolytic enzymes, aspartic proteases have been implicated in several plant development functions and are gaining more prominence due to their involvement in plant–pathogen interactions. In this review, we summarize the current knowledge on plant and pathogenic aspartic proteases and highlight the most recent findings on their participation on plant defense, as well as in pathogen infection strategies. Abstract: Plant aspartic proteases (APs; E.C.3.4.23) are a group of proteolytic enzymes widely Citation: Figueiredo, L.; Santos, R.B.; distributed among different species characterized by the conserved sequence Asp-Gly-Thr at the Figueiredo, A. Defense and Offense active site. With a broad spectrum of biological roles, plant APs are suggested to undergo functional Strategies: The Role of Aspartic specialization and to be crucial in developmental processes, such as in both biotic and abiotic Proteases in Plant–Pathogen stress responses. Over the last decade, an increasing number of publications highlighted the APs’ Interactions. Biology 2021, 10, 75. involvement in plant defense responses against a diversity of stresses. In contrast, few studies https://doi.org/10.3390/ regarding pathogen-secreted APs and AP inhibitors have been published so far. In this review, we biology10020075 provide a comprehensive picture of aspartic proteases from plant and pathogenic origins, focusing on their relevance and participation in defense and offense strategies in plant–pathogen interactions. Academic Editors: Maria Doroteia Campos, Maria do Rosário Félix and Gustavo Caetano-Anollés Keywords: proteases; development and reproduction; plant immunity; plant–pathogen interaction Received: 23 November 2020 Accepted: 19 January 2021 Published: 21 January 2021 1. The Past and the Present of Aspartic Proteases Publisher’s Note: MDPI stays neutral Aspartic proteases (APs) were first discovered in animals during the nineteenth century. with regard to jurisdictional claims in In 1836, Theodor Schwann described pepsin, which he identified during the study of animal published maps and institutional affil- gastric juices [1]. Later, in 1875, a pepsin-like proteinase was described in the pitcher plant iations. (Nepenthes) after treatment of the plants’ digestive juice with sulfuric acid [2]. Almost a century after the discovery of the first AP, in 1930, the purification and crystallization of swine pepsin by John Northrop provided a substantial evidence that proteases were proteins [3]. In the following years, other proteases were crystallized and studied, including chymotrypsin, Copyright: © 2021 by the authors. trypsin, and pepsinogen [4]. The conversion of pepsinogen to the active form of pepsin is Licensee MDPI, Basel, Switzerland. an autocatalytic process that occurs at a low pH (1.5–5). Based on these findings, in 1962, This article is an open access article the first step was taken towards the study of acidic proteinases [5]. In 1970, the discovery of distributed under the terms and pepstatin [6], a powerful inhibitor of aspartic proteases, encouraged its use as an immobilized conditions of the Creative Commons compound for affinity purification of these proteases [7,8]. A major breakthrough occurred Attribution (CC BY) license (https:// in 1972, when the complete amino acid sequence of the pig pepsin was uncovered [9]. Later, creativecommons.org/licenses/by/ in the 1980s, the current terminology of the aspartic (or aspartyl) proteases was established, 4.0/). Biology 2021, 10, 75. https://doi.org/10.3390/biology10020075 https://www.mdpi.com/journal/biology Biology 2021, 10, 75 2 of 14 Biology 2021, 10, x 2 of 14 resulting from the observation that the carboxyl groups belonging to aspartate residues were uncoveredinvolved in [9]. the Later, catalytic in the process 1980s, [10 the]. current terminology of the aspartic (or aspartyl) pro- teasesAlthough was established, most studies resulting about from APs the were observation performed that inthe mammals, carboxyl groups yeast, andbelonging fungi, tosome aspartate work residues has been were developed involved in in plants the catalytic [11]. Plant process APs [10]. were purified from the seeds of manyAlthough organisms, most studies such as aboutOryza APs sativa were[12 performed], Cucurbita in maximamammals,[13 ],yeast,Cucumis and fungi, sativus some[13], workTriticum has aestivumbeen developed[14], and in Hordeumplants [11]. vulgare Plant [APs15], were as well purified as from fromLycopersicon the seeds of esculentum many or- ganisms,leaves [16 such]. In as 1991, Oryza the sativa DNA [12], sequence Cucurbita ofmaxima the first [13], plant Cucumis aspartic sativus protease, [13], Triticum from aestivum barley [14],(Hordeurn and Hordeum vulgare), vulgare was sequenced [15], as well [17 as]. from In the Lycopersicon following years,esculentum APs leaves from other [16]. In organisms, 1991, the DNAincluding sequence one from of theArabidopsis first plant thaliana aspartic, wereprotease, isolated, from providing barley (Hordeurn more information vulgare), was about se- quencedplant APs’ [17]. structure In the followin [7]. g years, APs from other organisms, including one from Arabidop- sis thalianaAccording, were toisolated, the MEROPS providing database more information (http://www.merops.ac.uk about plant APs’ structure), aspartic [7]. proteases (EC 3.4.23)According are groupedto the MEROPS into 16 families,database based(http://www.merops.ac.uk), on similarities of the aminoaspartic acid proteases sequences (EC 3.4.23)of the are catalytic grouped site. into These 16 families, families based are clusteredon similarities into of five the different amino acid clans sequences that reflect of the a catalyticcommon site. evolutionary These families origin are and clustered similar into tertiary five different structure clans [18 ].that Plant reflect aspartic a common proteases evo- lutionaryare distributed origin among and similar 12 of thetertiary 16 families: structure A1, [18]. A2, Plant A3, A9, aspartic A11, A28,proteases andA32 are ofdistributed clan AA; amongfamilies 12 A22 of the and 16 A24 families: of clan A1, AD; A2, family A3, A9, A8 A11, and A28, A31 and of clan A32 AC of andclan AE,AA; respectively;families A22 and A24family of clan A36 AD; which family has notA8 yetand been A31 assignedof clan AC to and a clan AE, [19 respectively;]. A majority and of family plant APs A36 belongwhich hasto A1 not family yet been [20 assigned]. to a clan [19]. A majority of plant APs belong to A1 family [20]. InIn 2004, 2004, with with the the completion completion of of ArabidopsisArabidopsis genome,genome, new new perspectives perspectives have have risen risen re- gardingregarding plant plant APs’ APs’ diversity diversity [21]. [21 The]. The first first plant plant aspartic aspartic protease protease gene gene family family to be to de- be scribeddescribed belonged belonged to Arabidopsis to Arabidopsis withwith 51 known 51 known genes genes [22]. [In22 ].the In following the following years, years,plant APsplant have APs been have found been foundin increa insing increasing numbers numbers [23] with [23 ]96 with OsAP 96 genesOsAP ingenes rice in(Oryza rice (sativaOryza) [24],sativa 50)[ 24VvAP], 50 genesVvAP ingenes grapevine in grapevine (Vitis vinifera (Vitis vinifera) [25], and)[25 67], and PtAP 67 genesPtAP genesidentified identified in black in cottonwoodblack cottonwood (Populus (Populus trichocarpa trichocarpa) [26]. )[ 26]. So far, far, it it is is known known that that plant plant APs APs are are involved involved in inseveral several cell cell mechanisms, mechanisms, from from de- velopmentaldevelopmental processes processes [27–29] [27– to29 ]abiotic to abiotic [30–32 [30] and–32] biotic and bioticstress stressresponses responses [33–35]. [33 Major–35]. milestonesMajor milestones concerning concerning aspartic aspartic proteases’ proteases’ history history and relation and relation to pathogen to pathogen resistance resistance are presentedare presented in Figure in Figure 1. 1. Figure 1. Aspartic proteases historical breakthroughs. AP, aspartic protease; CDR1, constitutive disease resistance 1; PSI, plant-specificplant-specific insert; AP13, aspartic protease 13; SA, salicylicsalicylic acid; AED1, apoplastic enhanced disease susceptibility 1; APCB1, aspartylaspartyl proteaseprotease cleaving cleaving bcl-2 bcl-2 associated associated athanogene; athanogene; BAG6, BAG6, BCL-2 BCL-2 associated associated athanogene athanogene protein protein 6; SA, 6; SA, salicylic sali- acid;cylic acid; JA, jasmonic
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