Tài liệu Báo cáo khoa học: Insights into and speculations about snake venom metalloproteinase (SVMP)

REVIEW ARTICLE

Insights into and speculations about snake venom

metalloproteinase (SVMP) synthesis, folding and disulfide

bond formation and their contribution to venom

complexity

Jay W. Fox1 and Solange M. T. Serrano2

1 Department of Microbiology, University of Virginia, Charlottesville, VA, USA

2 Laborato´rio Especial de Toxinologia Aplicada-CAT ⁄ CEPID, Instituto Butantan, Sao Paulo, Brazil

Introduction

Since the first discovery of zinc-dependent proteinases

in viperid snake venom, investigators have intensively

studied the structure and function of these proteinases

in order to understand their role in envenomation

pathologies [1]. With the advent of the first complete

sequence determination of these proteinases, it was

thought that they belonged to the matrix metallo￾proteinase family of proteinases [2]. However, it soon

became obvious that they in fact comprised a novel

family of metalloproteinases, the M12 family, to which

the ‘a disintegrin and metalloproteinase’ (ADAM)

proteins also belong [3]. As studies progressed, the

snake venom metalloproteinases (SVMPs), as this

group of proteinases is now named, were further cate￾gorized into the PI, PIIa and PIIb, PIIIa and PIIIb,

and PIV classes [4,5]. The criterion for this differential

classification essentially was based on the presence or

absence of various nonproteinase domains as observed

via mRNA transcripts and proteins isolated in the

venom. To date, no PIV mRNA transcript has been

observed, and thus it very well may be that the PIV

structure simply represents another post-translational

modification of the canonical PIII structure; therefore,

in our new classification scheme, we have collapsed the

Keywords

autolysis; disintegrin; disulfide bond;

metalloproteinase; post-translational

processing; proteome snake venom;

structure; SVMP transcriptome

Correspondence

J. W. Fox, Department of Microbiology,

University of Virginia, PO Box 800734,

Charlottesville, VA 229080734, USA

Fax: +1 434 982 2514

Tel: +1 434 924 0050

E-mail: [email protected]

(Received 4 February 2008, revised 27

March 2008, accepted 15 April 2008)

doi:10.1111/j.1742-4658.2008.06466.x

As more data are generated from proteome and transcriptome analyses of

snake venoms, we are gaining an appreciation of the complexity of the

venoms and, to some degree, the various sources of such complexity. How￾ever, our knowledge is still far from complete. The translation of genetic

information from the snake genome to the transcriptome and ultimately

the proteome is only beginning to be appreciated, and will require signifi￾cantly more investigation of the snake venom genomic structure prior to a

complete understanding of the genesis of venom composition. Venom com￾plexity, however, is derived not only from the venom genomic structure

but also from transcriptome generation and translation and, perhaps most

importantly, post-translation modification of the nascent venom proteome.

In this review, we examine the snake venom metalloproteinases, some of

the predominant components in viperid venoms, with regard to possible

synthesis and post-translational mechanisms that contribute to venom com￾plexity. The aim of this review is to highlight the state of our knowledge

on snake venom metalloproteinase post-translational processing and to

suggest testable hypotheses regarding the cellular mechanisms associated

with snake venom metalloproteinase complexity in venoms.

Abbreviations

ER, endoplasmic reticulum; MMP, matrix metalloproteinase.

3016 FEBS Journal 275 (2008) 3016–3030 ª 2008 The Authors Journal compilation ª 2008 FEBS